IndraLab

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EGFR activates STAT3. 565 / 593
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"In this regard, epidermal growth factor receptor mediated activation of Stat3 occurrs in mouse epidermis following topical treatment of diverse classes of tumor promoters, including TPA, okadaic acid, and chrysarobin."
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"EGFR amplifies EGF signals to activate MMP-9 and the ERK1/2, PI3K and AKT, STAT3, and STAT5 pathways."
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"The relationship between LIF- and EGFR-induced STAT3 activation is also found in various types of cells, such as lung carcinoma cells [ xref ] and ovarian cancer cell lines [ xref ]."
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"While it is well established that EGFR can activate STAT3, STAT1 activation by EGFR has been reported rarely in the literature and primarily in cells that overexpress EGFR ( xref )."
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"Full-length EGFR binds and directly activates signal transducer and activator of transcription 1 (STAT1) and STAT3 (David et al, 1996); these function as homo- and heterodimers (Stancito et al, 1996; Sato et al, 1997)."
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"These studies support the role of Stat3 as an oncogene, which is activated early in SCCHN carcinogenesis, and efforts to understand EGFR mediated Stat3 signaling could facilitate novel strategies that will interfere with this growth promoting pathway."
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"FIP-nha, a fungal immunomodulatory protein from Nectria haematococca, induces apoptosis and autophagy in human gastric cancer cells via blocking the EGFR-mediated STAT3/Akt signaling pathway."
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"The binding of EGF to its receptor represented one of the first events identified as being capable of inducing robust activation of STAT3. xref Indeed, the activation of STAT3 by EGF receptor (EGFR) requires Src to phosphorylate the catalytic domain of EGFR at Tyr845, as well as at two EGFR autophosphorylation sites located at Tyr1068 and Tyr1086, both of which serve as docking sites for STAT3. xref , xref Moreover, EGF simulation of carcinoma cells that express aberrantly high levels of EGFR is sufficient to induce EMT phenotypes. xref Along these lines, Lo and colleagues xref demonstrated that the ability of EGF to induce EMT programs was contingent upon the activation of STAT3 in human tumors that harbored genomic amplifications of EGFR."
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"Stat3 activation by the EGFR has been mapped to the COOH-terminal region of the EGFR between amino acid residues 1061 and 1123, which contains Y1068 and Y1086."
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"For example, whereas the direct activation of STAT3 by EGFR has been clearly shown in HNSCC cells, STAT3 can also be activated by an EGFR independent mechanism."
18805044
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"These include for example the epidermal growth factor receptor (EGFR) or the cytokine β-receptor gp130 where the EGFR increased AKT-mTOR and STAT3 induction."
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"Our results identify a novel mechanism of EGFR-activated STAT3, in which TRIM59 maintains oncogenic signaling by inhibiting STAT3-TC45 complex formation to keep STAT3 phosphorylation and activation."
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"XREF_BIBR, XREF_BIBR EGFR induced STAT3 signaling initiates transcription of genes necessary for cell growth (Cyclin D1), survival (Bcl-X L) and angiogenesis (VEGF)."
20038820
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"IL-6, Janus-activated kinases (JAK), epidermal growth factor receptor (EGFR), and Src family kinases activate STAT3."
24875648
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"EGFR/EGFRvIII-dependent up-regulation of STAT3 is essential for the activation of cyclooxygenase-2 (COX2) transcription ( Lo et al., 2010 )."
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"This soluble form of HB-EGF then binds to and initiates phosphorylation of EGFR and subsequently activates STAT1 and STAT3 (XREF_FIG)."
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"[22] SARS-CoV-2 infection causes activation of aberrant STAT pathway which results in an acute lung injury upregulating EGFR that leads to constitutive STAT3 activation."
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"EGFR/EGFRvIII-dependent up-regulation of STAT3 is essential for the activation of cyclooxygenase-2 (COX2) transcription ( Lo et al., 2010 )."
28583430
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"During VACV infection, VGF induces epidermal growth factor receptor (EGFR) signaling to activate the noncanonical signal transducer and activator of transcription 3 (STAT3) pathway (Fig. 3C) ."
35073751
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"In medulloblastoma, Kotipatruni et al. (2012) detected that EGFR-induced STAT3 could be involved in the up-regulation of uPA and matrix metalloproteinase (MMP)-9 and further inhibition of apoptosis."
28583430
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"XREF_BIBR, XREF_BIBR, XREF_BIBR In this regard, the previously demonstrated overexpression of EGFR and its ligands in the tumor cells of specific subtypes of SGTs, including salivary duct carcinoma, mucoepidermoid carcinoma, and adenoid cystic carcinoma, may drive constitutive Stat3 signaling in these tumors."
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"In lung adenocarcinomas, STAT3 can be activated by mutant EGFR via driving the expression of the IL-6 cytokine, which activates the gp130/JAK signaling pathway, while blocking this pathway will repress cell-cycle progression, cell growth, and tumorigenesis [ xref ]."
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"Also, further targets of the transcriptionally active heterodimer EGFRvIII/STAT5 are needed to be identified, it is clear that both EGFRvIII-activated STAT3 and STAT5 are involved in the induction of [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Notably, EGFRvIII-induced STAT-3 signaling is not unique for mediating the pathogenesis of GBM but can be also involved in the development of other tumors such as breast carcinoma ( Han et al., 2013; [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
28583430
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"Importantly, iNOS mediates EGFRvIII induced STAT3 dependent proliferation of astrocytes."
22674257
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"RRAD promotes EGFR mediated STAT3 activation and induces temozolomide resistance of malignant glioblastoma."
25313011
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"A recent study found that arsenic exposure can lead to IL-8 overexpression via the phosphorylation of human epidermal growth factor receptor 2 (HER2), promoting migration and EMT while activating ERK (extracellular signal-regulated kinase), AKT, and STAT3 (signal transducer and activator of transcription 3) signaling pathways to increase cancer stem cell markers such as CD44 in bladder epithelial cells."
| PMC
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"Whether EGFRvIII triggers a transcriptional switch in STAT3 function outside of the brain will be an important question for future studies."
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"Thus, EGFR could also mediate the STAT3 activation in EBV-positive T- or NK-cells."
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"Using the knowledge that EGFRvIII activates the transcription factor STAT3, they simultaneously performed RNA-seq on mouse astrocytes (one of the normal cells of origin for HGG) expressing EGFRvIII in the presence or absence of Stat3 ."
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"Unlike ligand activated wild-type EGFR, however, EGFRvIII also activates the c-Jun N-terminal kinase through PI3K, but can not activate the signal transducers and activators of transcription 1 (STAT1) and STAT3 [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"The epidermal growth factor receptor (EGFR), a member of the ErbB/HER family, activates intracellular signaling pathways such as RAS/RAF/MEK/ERK, PI3K/AKT, and JAK/STAT3, which are involved in regulating cellular growth, survival, and migration."
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"P-STAT-3 is constitutively activated by aberrant EGFR signaling and IL-6 in human glioblastoma tissues [6] , as assessed by both tyrosine and serine phosphorylation."
21684758
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"Increased EGFR activity has been demonstrated to promote persistent activation of STAT3, which leads to tumor progression."
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"EGFR can activate STAT3 through JAK-dependent pathway."
33753143
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"SI-2 markedly reduced phosphorylation of EGFR and inhibited activation of AKT and STAT3."
20166659
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"12 Interleukin 6 (IL-6), Janus activated kinases (JAK), EGFR, and Src family kinases are among the activators of Stat3."
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"Indeed, time-course simulations showed that EGFR-PYK2 co-inhibition was synergistic because it eliminated the adverse network rewiring and reactivation of STAT3 and ERK caused by either EGFR or PYK2 inhibition alone ."
35582276
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"Our study showed that the chemical components of Sedanolide, Ligustilide, α-Terpineol, 4-Terpineol, Senkyunolide H, and Senkyunolide I in JBOL might act on the signaling pathway such as AGE-RAGE, EGFR, PI3K-Akt, and HIF-1 by modulating AKT1, STAT3, EGFR, IL-1β, and SCR, thus exerting an anti-IPF effect."
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"We showed that CDK5 regulates glioma tumorigenicity by promoting TRIM59 nuclear translocation via PIN1/importin α5 axis, leading to STAT3 signaling activation, and demonstrate that CDK5 mediates EGFR-stimulated STAT3 signaling through activation of the TRIM59/mH2A1 axis in GBM.This study identified and validated TRIM59 as a novel substrate of CDK5."
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"IGFBP-2 mediates EGFR-dependent STAT3 activation in glioblastoma cells."
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"15d-PGJ 2 does not inhibit EGFR mediated Stat3 signalling."
15316561
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"To assess the effect of 15d-PGJ 2 on EGFR mediated activation of Stat3, oral SCC cells were stimulated with exogenous TGF-alpha in the presence or absence of 15d-PGJ 2."
15316561
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"NO induced EGFR and Src activation subsequently activated Akt, c-Myc, STAT3 and beta-catenin pathways."
22878588
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"These results encourage the potential of utilizing PGG in combination with conventional therapy to enhance the efficacy of cancer treatment.HNSCC cells frequently overexpress EGFR and ErbB2 receptors, which activate STAT3 [24,31]."
35890129
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"However, recent evidence points to the contribution of Src in EGFR mediated Stat3 activation (Xi et al, 2003) and supports the existence of EGFR independent Stat3 oncogenic properties (Kijima et al, 2002)."
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"EGFR is overexpressed in at least one-half of all PC xref , xref and correlates with poor prognosis. xref , xref It has been reported that EGFR activates Stat3 in various types of cancers including PC. xref , xref Stat3 has been linked to the PC development and metastasis through the induction of various genes responsible for tumor cell proliferation, cell survival, and carcinogenesis. xref , xref , xref Maximum activation of Stat3 requires its phosphorylation at both of the residues (Tyr705 and Ser727)."
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"Inhibition of the EGFR or TGFalpha depletion in HNSCC resulted in growth inhibition and diminished STAT3 DNA binding activity [XREF_BIBR]."
27027445
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"Augmented activity of trans-membrane receptor associated TKs, such as EGFR, HER-2, and PDGFR, promotes STAT3 persistent activation, which contribute to oncogenesis or tumor progression ( Bromberg, 200[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"EGFR also activates transcription factor STAT3 (signal transducer and activator of transcription-3), which induces Twist expression necessary to induce autocrine TGF-β signaling ( xref )."
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"Cetuximab, by blocking the ligand-to-receptor access, prevents compensatory EGFR activation and phosphorylation of STAT3 [ xref ] in response to radiation induced damage."
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"Park OK, Schaefer TS, Nathans D: In vitro activation of STAT3 by epidermal growth factor receptor kinase."
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"Specific inhibition of EGFR failed to prevent STAT3 activation in some HNSCC cell lines; rather, an autocrine and paracrine IL-6 and gp130 loop was demonstrated in these cell lines [XREF_BIBR]."
27027445
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"STAT1 and STAT3 play opposing roles in the course of oncogenesis and tumor progression, and an imbalance in STAT1 vs STAT3 signaling is observed in many epithelial cancers, in particular in settings in which EGFR simultaneously activates STAT3 while inhibiting STAT1 via SHP2."
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"Ponatinib, as a lead candidate, inhibits STAT3 activity driven by EGF/EGFR, IL-6/IL-6R, and IL-11/IL-11R."
36286020
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"Interestingly, researchers revealed that NCAPG participates in trastuzumab resistance in human epidermal growth factor receptor 2 (HER2)-positive breast cancer via activating SRC/STAT3 signaling axis (11)."
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"And repressed GPRC5A correlates with activated EGFR and STAT3 signaling in lung cancer [XREF_BIBR], which explains dysregulated STAT3 induced by aberrantly activated EGFR in lung cancer."
28270740
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"EGFR phosphorylation activates downstream signaling pathways and increases STAT3 (Lv et al., 2017), AKT (He et al., 2018)and ERK1/2 (Zhou et al., 2020) phosphorylation levels."
37077419
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"However, endothelial growth factor receptor (EGFR), which could activate STAT3, has been implicated both in the inherent and acquired resistance to sorafenib [XREF_BIBR, XREF_BIBR]."
24418169
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"SIE reporter assays showed that PIAS3 served as a potent inhibitor for STAT3 by not only inhibiting constitutive STAT3 activity but also impairing EGFR induced STAT3 transcription activation."
29950561
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"53 As AKT is also downstream of EGFR, EGFR can activate STAT3 through multiple downstream effectors."
29321659
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"Expression of miR-21 can be influenced by gene amplification 12, transcriptional silencing 39, genotoxic stress (i.e. H 2 O 2 or ionizing radiation) 40, and various other transcriptional mechanisms including activation by EGFR pathway 41, STAT3 dependent regulation through interleukin 6 (IL-6) 42 or interferon (IFN) 43 and transcriptional repression by FOXO3A 44."
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"The findings reveal a novel mechanism where H3K23ac/TRIM24 mediates EGFR-induced STAT3 activation, enhancing the oncogenic potential of the EGFR/STAT3 pathway in human cancer [ xref ]."
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"Signatures scoring different pathways were also concordant; for instance, Myc mediated regulation of E2F signaling 33 was identified by the association between the RB-LOH 16 and Myc 15 signatures (R = 0.79), while EGFR mediated activation of Stat3 signaling 34 was recapitulated by the EGFR XREF_BIBR, XREF_BIBR and Stat3 XREF_BIBR, XREF_BIBR (R = 0.72) signatures."
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"Inhibition of epidermal growth factor receptor (EGFR) and Src activities by the inhibitors PD-153035 and PP2, respectively, abolished the activation of Stat3 by DEP, suggesting that Stat3 activation by DEP requires EGFR and Src kinase activation."
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"Even though Stat3 and Stat5 transcription factors are activated by cell surface bound EGF receptor, it is unclear through which route these factors that regulate transcription of major anti-apoptotic [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In vitro activation of Stat3 by epidermal growth factor receptor kinase."
9442382
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"STAT1 and STAT3 play opposing roles in the course of oncogenesis and tumor progression, and an imbalance in STAT1 vs STAT3 signaling is observed in many epithelial cancers, in particular in settings in which EGFR simultaneously activates STAT3 while inhibiting STAT1 via SHP2."
24501692
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"This elevated expression of CYP3A5 is attributed to transcription factor STAT3 activated by EGFR signaling or TMZ treatment."
39754188
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"Therefore, concurrent inhibition of both EGFR and TrkA is necessary to sufficiently attenuate STAT3 signaling and induce a significant response in HNSCC."
31838083
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"Inhibiting EGFR can enhance STAT1 signaling, hence stimulating TAA presentation, and inhibit STAT3, hence favoring the conversion of an immunosuppressive tumor microenvironment into an immunostimulatory one."
24501692
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"Satoh et al. provide further evidence that STAT3 signaling in TECs is induced by the epithelial growth factor receptor (EGFR), although the intrathymic physiological source of its ligand remains uncle[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29236672
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"In many tumors, overexpression of EGFR can stimulate various intracellular signaling cascades that lead to activation of a number of transcription factors, including and NF-κB and STAT3 that leads to [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
20079806
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"The current study suggests that the EGFR induced activation of STAT3 is more complicated than thought previously."
15950906
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"In addition to the traditional pathway in which EGFR activates STAT3 and activated STAT3, in turn, translocates into the nucleus to turn on gene expression, another mode of regulation could be derived[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
15950906
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"Mechanistically, HDAC8 promoted EMT by inducing the phosphorylation of EGFR and in turn led to the activation of its downstream fibrotic signaling pathways, including STAT3/HIF-1α and ERK1/2."
36911746
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"STAT3 and STAT5 are activated by EGFR or Jak pathway; then the STAT3/5 undergoes dimerization and induces proteins in cancer progression ( Loh et al., 2019 )."
32619673
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"Then, EGFR stimulates STAT3 signaling that in turn, leads to upregulation of Twist as EMT-TFs."
35716914
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"The role of STAT3 in HPV positive and negative oral lesions was evaluated further by examining level of pEGFR (Y1092) that activates STAT3 28 and p16, a negative regulator of STAT3 29 and an established surrogate marker for HPV infection 7."
28155253
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"Epidermal growth factor receptor mediated activation of Stat3 during multistage skin carcinogenesis."
15059889
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"In cancer cells with high MET activity, inhibition of EGFR activity alone likely is not sufficient to abrogate STAT3 activity."
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"The aberrant STAT pathway was activated by the SARS-CoV-2 infection, which mediates an acute lung injury, elevating EGFR that results in the activation of STAT3."
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"Moreover, significantly decreased expression of EGFR, phosphorylated Stat3 and c‐Myc, and significantly increased expression of p27 have been found in ECSCs. xref Mechanistically, EGFR activates Stat3, and phosphorylated Stat3 enters the nucleus to promote c‐Myc expression, which inhibits p27. xref p27 is a cyclin‐dependent kinase (CDK) inhibitor that restricts cell cycle progression by arresting cells in G1 phase. xref Tong et al revealed that low p27 expression may alter the cell cycle to make esophageal cancer cells more resistant to radiation. xref This process suggests that the EGFR/Stat3/c‐Myc/p27 pathway may contribute to the quiescence of ECSCs. xref , xref "
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"However, our data could not exclude an EGFR independent activation of STAT3 [ xref ] under the pepsin-effect which may be clarified by further exploration."
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"STAT3 can be also activated by EGFR, JAK2, and other tyrosine kinases activated by EGF, leukemia inhibitory factor (LIF), and other cytokines ( xref )."
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"Experimental models have also indicated that gefitinib (EGFR TKI) treatment increases AKR1B1, p-STAT3, and SLC7A11 proteins, whereas this phenomenon is abolished by epalrestat treatment."
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"In H1650 cells, where mutated epidermal growth factor receptor (EGFR) constitutively activated STAT3 via SFKs, this compound reduced STAT3 phosphorylation without reduction of SFK phosphorylation, indicating that this compound could inhibit STAT3 phosphorylation independently of the type of upstream kinases (XREF_FIG)."
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"While it is well established that EGFR can activate STAT3, STAT1 activation by EGFR has been reported rarely in the literature and primarily in cells that overexpress EGFR."
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"The epidermal growth factor receptor ( EGFR ) , which activates STAT3 , is reportedly overexpressed in human pancreatic cancer cells [ 7 ] ."
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"The epidermal growth factor receptor (EGFR) can activate STAT1, STAT3, and STAT5; in the same way, the platelet-derived growth factor receptor (PDGFR) directly activates STAT5 [68,69,70]."
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"In HeLa cells, along with c-Src, Pyk2 can facilitate EGFR mediated STAT3 activation [XREF_BIBR]."
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"ROS produced by this oxidase activates Src, enable that in turn, transactivates EGFR that activates Stat3 in tyrosine, allowing its dimerization."
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"Importantly, the activation of REG3A, as a secreted protein, may be through binding with EGFR in turn enhancing JAK2/STAT3 pathway to constitute a REG3A–JAK2/STAT3 positive feedback loop, which leads [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25779676
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"To verify this hypothesis, we focused on different interventions aimed at blocking Stat3 activation in MDA-MB-231 cells, in which constitutive Stat3 activation [10] is also most likely driven by EGFr [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17920763
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"A second member of the EGFR family, the ErbB2 receptor, also activates Stat3 in a Src and Jak2 dependent manner [53] ."
18621135
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"Phosphorylation of Y1068 in EGFR is required for EGFR-mediated STAT3 and ERK activation."
36410436
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"Furthermore, the EGF-initiated EGFR/STAT3 signaling pathway has been shown to induce the upregulation of TMEM16A, thereby activating STAT3 signaling in breast cancer cells [27]."
39563381
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"EGFR independent constitutive activation of STAT3 in head and neck cancers can also be mediated by IL-6 48."
28155253
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"A recent review pointed out that CD109 affects the activation of signal transducer and activator of transcription factor 3 (STAT3), which might be mediated by epidermal growth factor receptor (EGFR)."
32507856
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"Taken together, these data suggested that CD109 may be involved in the induction of EGFR-mediated STAT3 phosphorylation.To further determine the effects of EGFR in mediating CD109/STAT3 activity, the sorted CD109( + ) CaSki cells were treated with anti-EGFR antibody (2 µl/ml, Cetuximab, Cat."
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"In addition to being downstream of cytokine receptors, STAT3 is activated by growth factor receptor and non-receptor tyrosine kinases ( xref )."
19851315
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"IL-13Ralpha2 and EGFRvIII enhances activation of MAPK and STAT3."
29203859
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"Sang et al. revealed that EGFR-dependent Cdk5 triggers STAT3 signaling."
39668430
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"Then, CD109 was assumed to potentially facilitate STAT3 signalling that would be mediated by EGFR dimerisation."
32507856
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"Hence, EGFR and STAT3 might be the key effectors of the CD109-induced EGFR/STAT3 signalling network regulating the maintenance of CSC properties.To examine whether CD109-induced EGFR-mediated STAT3 activation could contribute to the stemness-related regulation of CSCs, we performed anti-EGFR antibody treatment and siRNA STAT3 knockdown in sorted CD109( + ) CaSki cells, followed by in vitro functional assays."
32507856
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"To sum up, those findings suggested that CD109 induced EGFR-mediated STAT3 activation response for cell migrative and proliferative functions, and CSC phenotype maintenance in cervical cancer cell lines."
32507856
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"Amann et al. reported that IC50 of TKIs showed a more closely correlation with the inhibition of ERK and Akt phosphorylation and also pointed that inhibition of EGFR tyrosine kinase activity by means of gefitinib inhibits downstream STAT3 activity XREF_BIBR."
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"Moreover, CD109 is responsible for the induction of EGFR-mediated STAT3 regulation in cancer tumorigenicity and aggressiveness, which might reveal a potential molecular target for the development of an effective therapeutic strategy against cervical squamous cell carcinoma."
32507856
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"EGFR and IL-6R signaling cross-talk through JAK2 and STAT3 to mediate EMT in ovarian carcinomas; activated STAT3 in high-grade ovarian carcinomas may occur directly through activation of EGFR and IL-6R or indirectly through induction of IL-6R signaling."
25566498
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"Moreover, this result was correlated with the further phosphorylation of EGFR induced by TGF-beta1, which activates the STAT-3 signaling pathway, and consequently reduces the MMP-9 expression [XREF_BIBR]."
24368426
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"Activation of signal transducer and activator of transcription-3 (STAT3) and Jun by α6β4-ERBB2 (EGFR) causes cell polarity loss and hyperproliferation, respectively [63]."
37444576
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"XREF_BIBR, XREF_BIBR It has been reported that EGFR activates Stat3 in various types of cancers including PC."
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"Although EGFR can also signal to STAT3 ( Quesnelle et al., 2007 ), pharmacological inhibition of its tyrosine kinase activity did not prevent STAT3 phosphorylation in lung cancer cells, while it signi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18167335
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"Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas."
24709421
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"Blockade of EGFR activation inhibited the activation of both AKT and Stat3 in U87 and D54 GBM cells and induced spontaneous apoptosis, which were associated with reduction in the steady-state level of Mcl-1."
16007122
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"A newly identified EGFR variant, termed EGFRvA [XREF_BIBR], also drives STAT3 activation, as does a reported EGFR-SEPT14 chimera [XREF_BIBR]."
25262780
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"In vitro data show that EGFR blockade decreased STAT3 activation."
19569236
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"In addition to IL-6 signaling, STAT3 can be activated by EGFR, PDGFR, and Src kinase."
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"Because Stat3 can be activated by both EGF receptor and c-src, mCripto-1 deletion may reduce Stat3 signaling."
26429739
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"Full-length EGFR binds and directly activates signal transducer and activator of transcription 1 (STAT1) and STAT3 ( xref ); these function as homo- and heterodimers ( xref ; xref )."
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"STAT3 can be activated by both JAK and EGFR (via Src) signaling, subsequently binding target DNA to regulate gene expression [89,90]."
37511453
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"Moreover, EGFR also promotes transcriptional activation of signal transducer and activator of transcription 3 (STAT3) in the nucleus via direct interaction and enhances its biological functions such as tumor growth, differentiation, and apoptosis ( Figure 2 )."
37560308
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"Using the knowledge that EGFRvIII activates the transcription factor STAT3, they simultaneously performed RNA-seq on mouse astrocytes (one of the normal cells of origin for HGG) expressing EGFRvIII in the presence or absence of Stat3."
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"STAT3 can be activated by EGFR or IL-6."
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"It was reported that in tumor cells, EGFR is capable of activating STAT3; compared with IL-6, which mediates STAT3 activation rapidly and transiently, EGFR-mediated STAT3 activation is persistent xref ."
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"But our results did not show if STAT3 was directly activated by EGFR during carcinogenesis."
26028817
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"STAT3 can be activated by EGFR, JAK2, and other tyrosine kinases whose activation can be mediated by EGF, leukemia inhibitory factor (LIF), and other cytokines ( xref , xref , xref )."
18829483
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"In studies conducted during the early phase of T. gondii infection, we showed that invasion by T. gondii causes epidermal growth factor receptor (EGFR) signalling in various cell types from humans and rodents (epithelial cells, endothelial cells, and microglia), and two signalling pathways downstream of EGFR signalling enable the parasite to activate Akt and STAT3, negative regulators of autophagy that protect the parasite from initial targeting by autophagy (Muniz‐Feliciano et al., 2013; Portillo et al., 2017)."
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"Given that STAT3 is activated by EGFR and IL-6, we selected two NSCLC cell lines (H1650 and A549) with different PIAS3 expression levels to determine the effect of EGFR and IL-6 stimulation on PIAS3 interaction with STAT3."
19569236
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"In addition, EGFR and IL-6 signaling could in turn activate STAT3 after treatment with erlotinib [35]."
32872659
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"STAT3 can be directly catalyzed by either receptor tyrosine kinases (RTKs) (e.g., EGFR, KDR, and MET) or non-receptor tyrosine kinases (e.g., JAKs) (Butti et al., 2018)."
35559037
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"Compound 3 was 100-fold higher in the NIR cytoblot possibly due to the inability of the drug to penetrate the cell.The pathway analysis capability of the NIR cytoblot assay was further tested by exami[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
15707944
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"The JAK/STAT3 signaling pathway, activated by EGFR, promotes immunosuppression and resistance to anti-PD1 therapies."
40347254
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"STAT3 is activated by EGFR and HER2 and is activated in EGFR-mutated lung cancers and glioblastomas [39–42] ."
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"TMEM25 inhibits monomeric EGFR-mediated STAT3 activation in basal state to suppress triple-negative breast cancer progression."
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"It was more efficient in suppressing EGFR activation and phosphorylation of STAT3 compared with osimertinib treatment alone."
32355810
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"Here we report that EGFR monomer may activate signal transducer activator of transcription-3 (STAT3) in the absence of transmembrane protein TMEM25, whose expression is frequently decreased in human TNBC."
37095176
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"Similarly, berberine inhibited EGFR-induced STAT3 activity to increase gastric cancer sensitivity to the EGFR inhibitors cetuximab and erlotinib (148)."
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"EGF receptor and PDGF receptor can directly activate STAT3 ( xref ; xref )."
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"S1C), we investigated whether basal EGFR activity in the presence of the PDGFR inhibitor-IV contributes to cell shape change and STAT3 (Y705) nuclear translocation."
22213560
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"As we had previously shown that sustained Stat3 activation results in the desensitization of TGF-beta signaling in the IL-6 and gp130 signaling system, 21 we next set out to determine whether EGFR activated Stat3 in several human cell lines."
22751114
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"As shown in Figure 7A, reduction of EGFR markedly attenuated STAT3 activation induced by EGF."
34853810
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"Similarly, inhibition of EGFR by gefitinib treatment also significantly suppressed the activation of STAT3 in response to EGF in Tsc2 MEFs (Figure 7B)."
34853810
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"Moreover, EGF stimulation enhanced the activation of STAT3 induced by EGFR overexpression in Tsc1 MEFs (Figure 7C)."
34853810
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"In addition, IGFBP2 increased the nuclear amounts of the epidermal growth factor receptor (EGFR) to induce signal transducer and activator of transcription 3 (STAT3) that upregulates cyclooxygenase-2 (COX-2), which contributed to the generation of an immunosuppressive TME [16]."
36556226
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"After being phosphorylated, EGFR is activated and then in turn activates multiple downstream intracellular signaling pathways, mainly PI3K-Akt, STAT3, and Ras-Raf-MAPK pathways."
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"This warrants exploration into the significance of EGFR-mediated STAT3 activation in the dissemination of ovarian carcinoma."
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"Since STAT3 is activated by EGFR [ xref ], it further explains the observed decrease in both EGFR and STAT3 in BCC cells in response to silibinin and DHS treatments."
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"It is remarkable that monomeric EGFR specifically activates STAT3 but not STAT5."
37095176
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"Therefore, it is conceivable that the monomeric EGFR-mediated STAT3 activation might play a key role in promoting malignancy of TNBC.Loss-of-function mutations of tumor suppressor genes and gain-of-function mutations of proto-oncogenes are frequently involved in tumor development and progression."
37095176
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"In addition, an alternative strategy to block the monomeric EGFR-mediated hyperactivation of STAT3 could potentially be achieved by developing short peptides or small molecule compounds to block the interaction between EGFR and STAT3, which may provide lead compounds for TNBC drug development."
37095176
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"Moreover, inhibitors targeting STAT3 pathway upstream activators like EGFR, JAK, and IL-6 are also widely studied."
38615745
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"ZD6474 inhibits glioma cell proliferation and survival by suppressing phosphorylation of EGFRvIII and EGFRvIII activation of signal transducer and activator of transcription 3, Akt, extracellular signal-regulated kinase 1/2, and Bcl-X L ."
20371720
sparser
"Intriguingly, STAT3 activation by mutant- EGFR was initially believed to be direct."
32365499
reach
"These include lonafarnib (RAS inhibitor), omipalisib (PI3K inhibitor), pictilisib (PI3K inhibitor), RO5126766 (RAF and MEK inhibitor), sorafenib, because Ras/Raf/MAPK pathway [XREF_BIBR] and PI3K pathway [XREF_BIBR] are also involved in EGFR mediated STAT3 activation, these inhibitors can possibly synergistically potentiate IFN-I 's anti-SARS-CoV-2 activity."
33037393
sparser
"To determine whether STAT3 is differentially activated by EGFRvIII, we analyzed expression of tyrosine phosphorylated STAT3 by immunoblotting in addition to STAT3 transcriptional activity in the EGFRvIII-expressing HNSCC cells compared with vector-controls."
20622897
reach
"Inhibition of EGFRvIII phosphorylation by lapatinib and carnatinib strongly impaired the EGFRvIII-OSMR interaction and STAT3 activation."
27110918
sparser
"However, the changes in STAT3 activity were unexpected, as STAT3 is activated by erbB2 or EGFR in other cell types, not erbB4."
31291965
reach
"EGF-R mediated signaling is upstream of Stat3 activation and involved in the postnatal maintenance of the thymic medulla."
26789017
reach
"The combination treatment of TG101348 and erlotinib obviously decreased the expressions of EGFR, p-EGFR, Bcl-xL and survivin, suppressed the activation of STAT3, induced apoptosis and inhibited tumor growth of EGFR-mutant NSCLC cells in vivo."
25869210
reach
"For example, activation of fibroblast growth factor receptor-1 can induce SRC-mediated STAT3 activation, and increased expression of the epidermal growth factor receptor can also activate STAT3 signaling, thereby promoting the aerobic glycolytic pathway in cells [41,42]."
36291659
reach
"For example, the kinase PYK2 is recruited specifically to early endosomes, where it sustains EGFR-mediated STAT3 activation [ 39 ]."
26921695
reach
"Collectively, we showed that in the early stages following irradiation, RPRM deletion induced the upregulation of EGFR expression and promoted the phosphorylation of EGFR, which in turn promoted the activation of DNA‐PKcs and the STAT3‐Lin28a signaling pathway, resulting in more efficient DNA damage repair and better survival of HSCs."
36041213
reach
"Combined inhibition of Src and EGFR with gemcitabine inhibits constitutively activated STAT3."
21266529
reach
"Because the EGFR makes major contributions to STAT3 activation during tumor promotion, loss of CD151-integrin regulation of the EGFR should contribute to diminished STAT3 activation."
22824799
sparser
"Since signal transducer and activator of transcription 3 (STAT3) is activated by plasma membrane bound EGFR, the authors asked the question whether this association could also be found in the nucleus."
22127113
reach
"AZD1480 is another JAK1/2 tyrosine kinase inhibitor that has shown promising anti-tumor efficacy in an EGFR-driven model of lung adenocarcinoma by inhibiting STAT3 signaling [232,233] but lacked overall clinical activity in human NSCLC patients (NCT01219543 [214])."
| PMC
sparser
"Upon interaction with EGF, EGFR induces the phosphorylation and activation of signal transducer and activator of transcription 3 (STAT3), a transcription factor essential for cell survival and proliferation."
23737867
reach
"Additionally, epidermal growth factor receptor (EGFR) phosphorylation activates Janus kinase-2 (JAK2) and signal transduction, thus activating transcription 3 (STAT3) to results in the regulation of PD-L1 expression."
34576006
sparser
"Indeed, STAT3 can be activated by EGFR [25] , although NE did not activate STAT 3 in our experiments on the A549 cell line."
26610096
sparser
"Although a large body of knowledge has established the mechanisms by which EGFR activates STAT3 through JAK or Src xref , in this study, we show a novel mechanism by which activated EGFR enhances H3K23 acetylation and TRIM24 expression, promoting the association of TRIM24 with H3K23ac and STAT3, and facilitating STAT3 interaction with chromatin, leading to downstream signaling activation to drive glioma tumorigenesis."
29129908
sparser
"The epidermal growth factor receptor (EGFR) can activate STAT1, STAT3, and STAT5; in the same way, the platelet-derived growth factor receptor (PDGFR) directly activates STAT5 [ xref , xref , xref ]."
37372319
reach
"For instance, it has been reported that EGFR overexpression activates NF-κB and STAT3, leading to chemoresistance and poor prognosis in glioma and lung cancer [ 22 ]."
32610149
reach
"Previous studies have shown that EGFRvIII can promote EMT or cell invasion by activating STAT3 XREF_BIBR, XREF_BIBR or regulating myristoylated alanine rich protein kinase C substrate overexpression XREF_BIBR."
24376686
reach
"Since EGFR and IL-6 activate STAT3, STAT decoy oligonucleotides can be used in synergism with EGFR or IL-6 antagonists."
36683526
sparser
"Phosphorylation of EGFR at tyrosine 1068, a marker of EGFR activation, and phosphorylation of STAT3 at tyrosine 705, a marker of STAT3 activation, were stimulated by NTS administration (Supplementary Fig.  xref )."
29184126
reach
"Src kinase plays a vital role in EGFR mediated STAT3 and STAT5 activation in HNSCC."
20924973
reach
"In the present study, we further confirmed that STAT3 could be activated by EGFRvIII, and inhibition of STAT3 activation or knock down of STAT3 could inhibit S100A11 expression and S100A11 promoter activity."
24376686
reach
"Hence, we deduce that NOK delineates a specific activation pathway for EGFR to activate STAT3 and STAT5 during the tumorigenesis of breast cancers.We proposed that NOK is a co-receptor for EGFR and focused on the effect of NOK on the phosphorylation of EGFR."
39808846
reach
"83 Mechanistically, EGFR activates Stat3, and phosphorylated Stat3 enters the nucleus to promote c‐Myc expression, which inhibits p27."
34766149
reach
"A possible mechanism [24] involves EGFR activation of epithelial-mesenchymal transformation via protein kinases and STAT3 activation by leukocyte hormone-6 to promote brain metastasis in lung adenocarcinoma."
38605303
sparser
"We have previously shown that in the GBM cell line U87, Stat3 is activated by EGFR and that activated Stat3 suppresses the spontaneous apoptosis of U87 cells by upregulating the expression of the pro-survival protein Mcl-1 in vitro. xref In U87 cells, although the EGFR-activated PI3K-AKT pathway significantly contributes to the cell survival, Stat3 activation is critical for the suppression of spontaneous apoptosis in vitro. xref To define the role of constitutively activated Stat3 in the growth of GBM in vivo , we generated stable U87-derived clones expressing DN-Stat3 under a constitutive CMV-promoter. xref The constitutive DN-Stat3-expressing U87 cells-derived tumours grown in flanks of nude mice were significantly smaller than those derived from the parental or vector control cells (data not shown)."
19121577
reach
"EGFR also enables sustained IL-6-dependent STAT3 activation [31] and crosstalks with IL-6R [32]."
30243717
sparser
"Experiments in primary mammary epithelial cells and transfected COS-7 cells revealed a p44/42 MAPK and EGFR-dependent Stat3 activation."
15292206
reach
"For instance, TMEM25 inhibits EGFR-driven STAT3 activation in triple-negative breast cancer, and TMEM116 is crucial for lung cancer cell mobility and metastasis via the PDK1 pathway.29, 30 TMEM9A promotes breast cancer progression by activating the Wnt/β-Catenin pathway.31 Overall, TMEM proteins influence cell proliferation, epithelial-mesenchymal transition, invasion, migration, and immune modulation, highlighting their potential as therapeutic targets in cancer.32Although our study is the first to reveal the anti-tumor role of TMEM71 in NPC, several limitations exist."
39951856
sparser
"For instance, EGFRs can directly activate STAT1 and STAT3, whereas PDGFRs can activate STAT5 [34–36] ."
36410636
sparser
"To examine whether IL-6 and EGFR activate STAT3 in podocytes, we blocked IL-6 and EGFR in cultured primary podocytes and performed western blotting to determine STAT3 phosphorylation (Tyr705), which is a marker of STAT3 activation."
29184126
sparser
"In addition to STAT3, p-ERK1/2 and p-AKT can also be activated by EGFR; accordingly, we investigated whether these additional downstream effectors of p-EGFR signaling were reduced in 1,3,4- O -Bu 3 ManNAc-treated cells."
27613843
reach
"STAT3 can be activated by Janus kinases (JAKs), epidermal growth factor receptor (EGFR), and interleukin 6 (IL6), which are involved in a number of physiological and pathological processes, including cell survival, proliferation, transformation, apoptosis, as cellular immunity ."
36977736
reach
"Other investigators have reported similar findings, showing that STAT3 has been linked to EGFR, where EGFR can activate STAT3, thus contributing to cancer progression."
36977736
reach
"In contrast, low levels of EGFR do not activate Stat3, whereas only high levels of EGFR are capable of Stat3 activation."
22751114
reach
"In addition, EGFR is known to activate STAT3 signaling."
24520077
sparser
"Whether EGFR-dependent STAT3 activation plays a role in MPNST transformation is unknown."
23318430
reach
"In addition, EGFR, which is one of the receptor tyrosine kinases, can phosphorylate signal transducer and activate transcription 3 (STAT3)."
35116890
trips
"We conclude that SOCS-1 methylation status can differentially affect STAT3 activation by IL-6R and EGFR through JAK or MEK in different HNSCC and response to pharmacologic antagonists."
16432158
reach
"Our observation that the tumor associated overexpressed EGFR activates Stat3 persistently identifies EGFR as a physiologically relevant upstream molecular cause of Stat3 activation."
22751114
reach
"21 Indeed, EGFR mediated Stat3 activation also results in the desensitization of TGF-beta signaling in many tumor cell lines with EGFR overexpression."
22751114
reach
"Of crucial importance, both EGFR and the PI3K/Akt signaling pathway are activated in cSCC, subsequently increasing Stat3 activity to enhance cell proliferation and survival."
30707166
reach
"Our results indicate that EGFR inhibition is not sufficient to suppress STAT3 activity when converging p75NTR signaling is activated."
33351787
sparser
"STAT3 can be activated by EGFR or IL-6."
28032598
reach
"EGFR or HER2 may modulate the STAT3 signaling cascade to regulate stemness, proliferation, and survival of cancer and CSCs [ 15 ]."
32201081
reach
"EGFR activation induces STAT3 signaling."
24520077
reach
"First, it provides some clear molecular targets for treating EGFR driven tumors, namely, Stat3 and Smad7."
22751114
sparser
"These results revealed STAT3 activation by EGFR in tumor promoter-treated epidermis and in skin papillomas may be a critical event during mouse skin tumor promotion, possibly through regulation of keratinocyte proliferation [ xref , xref ]."
28625132
reach
"EGFR, like OSMR, is also known as a biomarker for cervical cancer and induces tumor progression and activation of STAT3 [64,65,66,67]."
36551576
reach
"Many studies found that STAT3 is activated by EGFR tyrosine kinases."
31464520
reach
"Surprisingly, Stat3 activation by high levels of EGFR is slower than the Erk1/2 or Akt activation (XREF_FIG)."
22751114
reach
"Furthermore, the high level of EGFR mediated Stat3 activation is persistent, unlike the transient nature of Erk1/2 and Akt activation."
22751114
reach
"Epidermal growth factor receptor (EGFR)-mediated activations of MAPK, PI3K, and STAT3 signaling pathways demonstrate important mechanisms by which various ligands (i.e., EGF, TGF-α, amphiregulin, etc.) influence tumor growth, survival, and metastasis [57,58,59]."
38539448
reach
"XREF_BIBR Indeed, the activation of STAT3 by EGF receptor (EGFR) requires Src to phosphorylate the catalytic domain of EGFR at Tyr845, as well as at two EGFR autophosphorylation sites located at Tyr1068 and Tyr1086, both of which serve as docking sites for STAT3."
24843831
reach
"We found that Ponatinib inhibits STAT3 activity driven by EGF and EGFR, IL-6 and IL-6R and IL-11 and IL-11R, three major ligand and receptor systems involved in CRC development and progression."
30572654
reach
"The YCU-H891 cells, in which the epidermal growth factor receptor (EGFR)-signal transducer and activator of transcription 3 (Stat3) pathway is constitutively activated, were more resistant to treatments with ATRA, 5-FU and the combination of both agents than YCU-N861 cells."
11927016
sparser
"STAT3 is activated by many cytokine and growth factor receptors."
24738058
sparser
"To investigate that, we analysed the activation status of JAK2/STAT3 in ovarian carcinoma specimens and correlated that to STAT3 activation in two ovarian cancer cell lines directly by EGFR or indirectly through IL-6R activation."
19088723
reach
"Then, increased EGFR expression led to the formation of a positive feedback loop to increase STAT3 activation ."
38689093
reach
"In vitro activation of STAT-3 by epidermal growth factor receptor kinase."
23134344
reach
"EGFR can activate STAT3 through JAK-dependent pathway."
33753143
sparser
"As a membrane protein, EGFR can activate intracellular signaling molecule STAT3, which functions as a transcription factor to carry EGFR signal to the nuclear and regulate target gene expression."
26550019
sparser
"It was reported that, in head and neck cancer cells in which activation of STAT3 by epidermal growth factor receptor (EGFR) protects against apoptosis, abrogation of STAT3 activity markedly enhanced c[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23402820
reach
"Thus, our data also suggest that MALT1 contributes to the EGFR dependent activation of STAT3 in vivo."
25982276
sparser
"We also found that epidermal growth factor (EGF) stimulation or L858R mutation in EGF receptor (EGFR) induced Stat3 activation as well as ERβ expression in lung cancer cells."
21546410
reach
"Moreover, to further explain the results, we performed Western blots with the 30% U87EGFRvIII mixture and found that EGFRvIII increased the expression of the transcription factors STAT3, EZH2, NF-kB, [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
27317648
reach
"Research has shown that cross talk between TAMs and tumor cells can regulate the induction of the pluripotent gene SOX-2 through EGF receptor-mediated STAT3 signaling activation, and plays a crucial role in the expansion of cancer stem cells, chemotherapy resistance, and immune exclusion [165]."
38693304
reach
"EGFR-mediated STAT3 signal also facilitates HCV replication by impairing IFN-α production [ 14 ]."
32298770
reach
"Moreover, the EGFR activates STAT3 in lung cancer cell lines XREF_BIBR and can promote tumor survival in vivo in NSCLC by signaling through STAT3 XREF_BIBR."
25926075
reach
"Firstly, we determined whether EGFR is responsible for activation of ERK and STAT3 and expression of COX-2 and eNOS in CLP induced AKI mice model."
29207668
sparser
"Our studies show that poultry dust extract controls the induction of immune and inflammatory mediator levels via a cellular pathway involving oxidative stress mediated STAT-3 activation by Tyk2 and EGFR tyrosine kinases."
31042082
reach
"Lo et al. demonstrated that EGF exposure induces EMT in breast cancer cells, and this phenotypic transition regulates EGFR mediated activation of STAT3 via STAT3 activated TWIST gene expression [XREF_BIBR]."
28271910
reach
"In the future, the combined application of anti-EGFR targeted therapies and STAT3 inhibitors could represent a promising investigational treatment strategy for patients with EGFR-positive gastric cancer.The widespread activation of STAT3 in tumor-infiltrating immune cells weakens innate and adaptive immune responses and facilitates immune evasion."
39309860
reach
"The EGFR phosphorylation can activates Janus kinase-2 (JAK2) and signal transduction, thereby activating STAT3 to results in the regulation of PD-L1 expression."
38361933
reach
"Thus, the increment of p‐STAT3, a well‐known downstream effector of IL‐6, may be induced by EGFR signaling, which can also activate STAT3 by phosphorylation."
35509206
reach
"EGFR-mutant NSCLC cells with increased EGFR tyrosine kinase activity excessively activate multiple EGFR-mediated downstream signaling pathways, such as MAPK, PI3K/AKT, and STAT3 pathways, consequently promoting the overexpression of CSC biomarkers and enhancing the stem-like properties of the cells [32,33,34,52]."
37298389
reach
"The EGFR- and CSF-1-mediated activation of STAT3 in tumor cells and tumor associated immune cells is one of the key mechanisms by which TAMs provide support to tumors.32 Although expression of EGFR in the peripheral area of the pLSCCs was not different compared with the central area, phospho-EGFR (pY1068) and phospho-STAT3 (Tyr705) expression in the peripheral area of pLSCCs were higher than in the central area."
26663681
reach
"Upregulated EGFR expression and activation of EGFR-mediated STAT3, RAS-ERK and PI3K-AKT pathways are frequently reported in HNSCC (Amornphimoltham et al., 2004; Geiger et al., 2016)."
37680708
reach
"It was reported that rhein also sensitizes human pancreatic cancer cells to epidermal growth factor receptor (EGFR) inhibitors by inhibiting the signal transducer and activator of transcription 3 (STA[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
33515540
sparser
"It has been demonstrated that the interaction between SOCS3 and the EGFR COOH-terminal domain inhibits STAT3 activation by EGFR [ xref ]."
37270563
sparser
"Previous results showed that STAT3 could be activated by EGFR to participate in oncogenesis and was simultaneously involved in angiogenesis, especially the expression of VEGF‐A. xref , xref In our study, gefitinib also inhibited the expression VEGF‐A in H3255 xenograft model."
32368855
reach
"Mechanistically, EGFR kinase activity mediated activation of ERK1/2 and STAT3 signaling pathways to induce inflammation and renal cell injury."
29207668
reach
"These findings demonstrated that combined Src and EGFR inhibition decreases p-STAT3 activity, which increases the microvascular density within PDAC tumors, which ultimately results in increased delivery of cytotoxic chemotherapy into the tumor mass.The above orthotopic PDAC studies were conducted on athymic nude mice."
36902166
reach
"Then EGFR can interact with STAT3 in the nucleus and promote STAT3 activation, leading to enhanced cell proliferation."
31991790
sparser
"EGFR‐activated STAT3, for example, is critical for lung cancer metastasis (Soon, Leong, Koh, & Tham, xref )."
33304472
sparser
"STAT3 is activated by EGFR and HER2 and is activated in EGFR-mutated lung cancers and glioblastomas [39–42] ."
17981505
reach
"It is unknown whether the SFK or downstream EGFR signaling is responsible for phosphorylating STAT3, as inhibitors of either SFK or EGFR abrogated STAT3 activation."
32462405
sparser
"Although the mechanisms by which peptides promote wound-healing are not fully characterized, some studies have demonstrated that HDPs such as β-defensins promote keratinocyte migration through phospho[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25113635
reach
"We propose that IRF3 is activated at the cell membrane and then translocates to the nucleus, partly analogous to the model described for EGFR mediated activation of STAT3 38."
25503978
sparser
"In addition to IL-6, STAT3 can be activated by EGFR in many cancer types (reviewed in [ xref ])."
29262529
reach
"Protein expression analysis demonstrated that immature testis xenografts were able to establish angiogenesis either through eNOS activation via VEGF and PI3K and AKT or through EGFR mediated STAT3 pathway."
28572601
sparser
"As nuclear localization proteins, EGFR/ EGFRvIII can activate STAT3 and STAT5 through its tyrosine kinase function during nuclear translocation and can act as transcription factors in the nucleus, interacting with RHA (RNA helicase A), E2F, and STAT3/5."
30662352
reach
"It has been reported that Bcl-xL is regulated by EGFR activated STAT3 to promote survival in head and neck cancer XREF_BIBR."
24621885
reach
"In contrast, malignant progression of the keratinocyte towards SCC is associated with negative MAPK regulation and EGFR induced STAT3 activation [XREF_BIBR - XREF_BIBR], which drives expression of multiple antiapoptotic molecules [XREF_BIBR, XREF_BIBR, XREF_BIBR - XREF_BIBR]."
27457246
reach
"Indeed, the autocrine activation of the gp130 cytokine receptor in HNSCC cells by tumor released cytokines, such as IL-6, can result in the EGFR independent activation of STAT3."
16984731
reach
"Transmembrane protein 25 abrogates monomeric EGFR-driven STAT3 activation in triple-negative breast cancer."
38532948
reach
"The angiogenesis in testis graft could be established either through eNOS activation via VEGF and PI3K and AKT or via EGFR- mediated STAT3 pathway."
28572601
reach
"They proved that lack of TMEM25 enables monomeric EGFR to activate STAT3 in a ligand‐independent fashion in preclinical TNBC models, suggesting the importance of blocking the monomeric EGFR/STAT3 signaling axis in TNBC."
38532948
reach
"As noted above, Jak kinases can phosphorylate Stat3, reinforcing Egfr mediated Stat3 activation."
27748759
reach
"On the other hand, forced expression of TMEM25 significantly downregulated EGFR‐driven STAT3 activation, indicating that TMEM25 may play a crucial role in abrogation of convergence of EGFR activation toward STAT3 phosphorylation."
38532948
reach
"However, STAT3 activation was found to be independent of EGF, JAK, and Src, while EGFR inhibition negated STAT3 activation in TMEM25 cells."
38532948
reach
"Thus II-6 mediated activation of P-Jak2 depends on EGFR mediated Stat3 activation in SCPs, and maintains viability of SCPs."
27748759
reach
"The apoptosis induced by targeting MMP-9 and uPAR was initiated by inhibiting epidermal growth factor receptor (EGFR) mediated activation of STAT3 and NF-kappaB related signaling molecules."
22984561
reach
"EGFR and IL-6 have both been shown to activate STAT3 (XREF_FIG), and the relative role of these ligands and their receptors may depend on epigenetic inactivation of SOCS-1, a gene involved in negative feedback of IL-6R-janus kinase mediated STAT3 activation [XREF_BIBR, XREF_BIBR]."
19570715
reach
"STAT3 can be activated by EGFR or IL-6."
26028817
reach
"It was reported that in tumor cells, EGFR is capable of activating STAT3; compared with IL-6, which mediates STAT3 activation rapidly and transiently, EGFR mediated STAT3 activation is persistent 13."
26028817
reach
"STAT3 is activated by receptor tyrosine kinases EGFR, HER2, fibroblast growth factor receptor (FGFR), IGFR, HGFR and platelet derived growth factor receptor (PDGFR), receptor associated kinases (JAK) and non receptor kinases (Src and Abl) through phosphorylation [XREF_BIBR, XREF_BIBR]."
24743778
reach
"It is worth mentioning that prior studies have shown that there is cross-talk between JAK and STAT and EGFR signalling in the regulation of hyperproliferation [XREF_BIBR], and that EGFR is an upstream activator of STAT3 that can mediate EGFR signalling [XREF_BIBR, XREF_BIBR, XREF_BIBR]; therefore, EGFR-TKIs may be able to inhibit STAT3 activation."
27688730
reach
"40 Here, we show EGFR expression is relevant to sphere formation, a surrogate of tumour initiation (XREF_FIG), and that EGFR levels and activity mediate downstream activation of Stat3 in vivo and in vitro (XREF_FIG)."
27748759
reach
"Since STAT3 is activated by EGFR and IL-6R, EGFR inhibition in combination with IL-6 antagonists [XREF_BIBR] or STAT decoy oligonucleotides [XREF_BIBR] holds potential for synergistic activity."
19570715
reach
"Sustained STAT3 activation in this process may be mediated by EGFR."
26028817
reach
"Grandis et al. aimed to demonstrate that EGFR mediated Stat3 activation contributed to the uncontrolled acceleration of tumor growth by an anti-apoptosis mechanism, and found that inhibition of Stat3 activation via a liposome mediated Stat3 antisense plasmid resulted in inhibited tumor growth and stimulated apoptosis in HNSCC xenograft models XREF_BIBR, XREF_BIBR."
25589895
reach
"In addition to IL-6, STAT3 can be activated by EGFR in many cancer types."
29262529
reach
"29 In this work, KIF22 interference notably repressed glycolysis in melanoma cells, evidenced by reduced levels of ECAR, lactate production, HK2, PKM2 and LDHA expression as well as elevated levels of OCR.Increasing evidence indicates that EGFR signaling is important for the regulation of multiple cellular processes and is abnormally activated in many tumors.30 Therefore, targeted therapy targeting the EGFR signaling has become the focus of drug development for cancer treatment.31 EGFR-mediated STAT3 signaling activation promotes the proliferation and glycolysis in various cancers.17 18 In the study of melanoma, several reports have demonstrated that the activation of EGFR/STAT3 signaling promotes the malignant progression of melanoma.32 33 It has been reported that KIF22 activates EGFR signaling, an effective target for melanoma.15 16 Based on these results, the authors demonstrated that KIF22 knockdown inhibited the EGFR/STAT3 signaling in A375 cells."
37944197
reach
"But our results did not show if STAT3 was directly activated by EGFR during carcinogenesis."
26028817
reach
"As a membrane protein, EGFR can activate intracellular signaling molecule STAT3, which functions as a transcription factor to carry EGFR signal to the nuclear and regulate target gene expression."
26550019
reach
"1 Because Stat3 can be activated by both EGF receptor and c-src, 54,55 mCripto-1 deletion may reduce Stat3 signaling."
26429739
reach
"We showed that in SCP, EGFR driven P-Stat3 stimulates II-6 secretion, and Il6 reinforced EGFR and Stat signalling (XREF_FIG)."
27748759
sparser
"Given that STAT3 is activated by EGFR and IL-6, we selected two NSCLC cell lines (H1650 and A549) with different PIAS3 expression levels to determine the effect of EGFR and IL-6 stimulation on PIAS3 interaction with STAT3."
19569236
reach
"Moreover, EGFR reduction represses IKKalpha deletion induced excessive ERK, Stat3 and c-Jun activities, and skin inflammation."
21566664
reach
"Erlotinib resistance involved the activation of STAT3 by EGFR signaling in osteosarcoma cells [96]."
36834846
reach
"These data indicate that honokiol induces glioma cell apoptosis in vivo via the regulation of the EGFR mediated STAT3 and JAK signaling pathway."
30587839
sparser
"We previously revealed signal transducer and activator of transcription 3 (Stat3) as a nodal convergence point between said signaling pathways proving that Stat3 is activated by one of the ErbBs' ligands, heregulin (HRG)β1 via ErbB2 and through the co-option of PR as a signaling molecule."
26340407
sparser
"However, the cells were pre-incubated with EGCG before the addition of TGF-α, resulting the inhibition of EGFR-dependent STAT3 activation subsequently retarded VEGF synthesis in the cancer cells."
21827739
reach
"Indeed, time dependent simulations backed up by experiments helped reveal that while inhibition of EGFR or PYK2 alone (by Gefitinib or PF396, respectively) only temporarily suppressed the activities of ERK and STAT3 which were subsequently restored to basal levels; this activity recovery was abolished by the combined treatment."
29920512
sparser
"Suppressor of cytokine signaling-1 (SOCS-1) has been implicated recently in the negative regulation of IL-6R/Janus-activated kinase (JAK)-mediated activation of STAT3, suggesting that SOCS-1 could affect alternative activation of STAT3 by EGFR, IL-6R, and associated kinases."
16432158
reach
"Activation of the EGF receptor (EGFR) induces activation of STAT3 and AKT signaling pathways."
26444028
reach
"Similar work by Yunping Luo et al. found that the crosstalk between TAMs and tumor cells can regulate the induction of pluripotency gene SOX-2 through EGFR mediated activation of STAT3 signaling [XREF_BIBR]."
23455077
sparser
"We conclude that SOCS-1 methylation status can differentially affect STAT3 activation by IL-6R and EGFR through JAK or MEK in different HNSCC and response to pharmacologic antagonists."
16432158
sparser
"Since STAT3 is activated by cytokine receptor-associated tyrosine kinases or growth factor receptor intrinsic tyrosine kinases, besides antagonizing the function of relevant kinases or receptors, targeting the over-expressed ligands that inappropriately stimulate the activation of STAT3 is also a promising strategy for glioma [ xref ]."
21906308
reach
"Activation of the EGF receptor (EGFR) induces activation of STAT3 and AKT signaling pathways."
26444028
sparser
"Hence, we deduce that NOK delineates a specific activation pathway for EGFR to activate STAT3 and STAT5 during the tumorigenesis of breast cancers."
39808846
reach
"For example, small molecule inhibitors of JAK, Src, Bcr-Abl, and EGFR have all been shown to block STAT3 signaling and induce tumor cell apoptosis (XREF_FIG) [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."
24675568
sparser
"Activated Her2 and EGFR recruit signaling complexes and activate STAT3 and ERKs."
18555493
reach
"EGFR can activate STAT-3 [19]."
39290346
reach
"In pancreatic cancers, inhibition of upstream EGFR and the Src and Jak kinases have been shown to inhibit transcriptional activity of STAT3 and its downstream targets [143,148]."
19466902
reach
"Indeed, the autocrine ac tivation of the gp130 cytokine receptor in HNSCC cells by tumor released cytokines, such as IL-6, can result in the EGFR independent activation of STAT3."
16984731
reach
"This process implies a synergy between IL‐25R and EGFR signal transduction, which finally mediates STAT3 activation and tumor development."
34128588
sparser
"Stat3 is activated by mutant EGFR and JAK, and notably, pStat3 is associated with tumor cell proliferation and angiogenesis [ xref ]."
30174790
sparser
"We conclude that NOK defines a specific activation pathway for EGFR to activate STAT3 and STAT5 during the tumorigenesis of breast cancers."
39808846
reach
"EGFR activation induces the constitutive activation of signal transducer and activator of transcription 3 (STAT3), a known oncogenic transcription factor."
28611673
sparser
"Moreover, EGFRvIII activates Stat3 and Stat5 to drive pro-tumorigenic phenotypes in GBM cells and Stat3 small molecule inhibitors reduced target gene expression in EGFR-driven NSCLC( xref , xref , xref )."
29724813
sparser
"Expression of EGFRvIII confers poor prognosis and enhances invasion in GBM and EGFR and EGFRvIII activate Stat3 and Stat5 in GBM( xref , xref )."
29724813
reach
"Sriuranpong and colleagues [ 96 ] demonstrated that the use of EGFR inhibitors did not affect the phosphorylation of STAT3 in head and neck squamous cell carcinoma (HNSCC) cells, thus indicating the E[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32325172
reach
"We observed a two-fold increase in nuclear p-STAT3 in PDX tumors treated with erlotinib (XREF_FIG), consistent with the STAT3 activation observed in EGFR-mutant NSCLC cell lines treated with an EGFR TKI."
25843712
reach
"Furthermore, SDC1 affects AKT and STAT3 signaling pathways activated by the EGF receptor in breast cancer stem cells from triple negative breast cancer [XREF_BIBR]."
32916872
reach
"Previous results showed that STAT3 could be activated by EGFR to participate in oncogenesis and was simultaneously involved in angiogenesis, especially the expression of VEGF-A.34, 35 In our study, gefitinib also inhibited the expression VEGF-A in H3255 xenograft model."
32368855
reach
"According to our previous study, 7 EGFR, functioning as a REG3A receptor, mediated the REG3A signal promoting human pancreatic cancer cell growth and JAK2 and STAT3 activation."
28880262
reach
"Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas."
20384432
sparser
"STAT3 can also be directly phosphorylated and activated by EGFR. xref Phosphorylation at Y705 by EGFR induces dimerization of STAT3. xref , xref AKT phosphorylation of EZH2, which mediates DNA methylation, could further activate STAT3. xref As AKT is also downstream of EGFR, EGFR can activate STAT3 through multiple downstream effectors."
29321659
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"EGFR activation can trigger several signaling pathways including extracellular signal-regulated kinase 1/2 (ERK1/2), signal transducer and activator of transcription 3 (STAT3), and c-Jun, which are al[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
20732323
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"For example, Lv et al. shows that TRIM24 is a transcriptional co-activator in EGFR-driven glioblastoma by which H3K23ac/TRIM24 mediates EGFR stimulation of STAT3 pathway [7]."
30922374
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"To confirm that EGFR driven STAT3 signaling is one of the key mechanisms, we added an EGFR specific inhibitor to Panc02 cell media."
28880262
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"In vitro activation of Stat3 by epidermal growth factor receptor kinase."
10757107
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"Thus, our data also suggest that MALT1 contributes to the EGFR-dependent activation of STAT3 in vivo ."
25982276
reach
"EGFR(Try1068/1086) and EGFR(Try1148) each mediates the GRB2/STAT3 and GRB2/ERK signaling, respectively, and is oncogenic, with GRB2 being a known therapeutic target of many solid tumors including breast cancers [56]."
38052106
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"EGFR can also bind to the STAT-3-SH2 domain and activate STAT-3 [ xref ]."
32741371
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"A previous study revealed that PPARgamma plays an important role in controlling the proliferation and differentiation of neural stem cells mediated by the regulation of epidermal growth factor receptor and activation of extracellular signal regulated kinase (ERK) as well as signal transducer and activator of transcription 3 (STAT-3) pathways [XREF_BIBR]."
24136217
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"This warrants exploration into the significance of EGFR mediated STAT3 activation in the dissemination of ovarian carcinoma."
19088723
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"These results clearly demonstrated that MET- and EGFR mediated STAT3 signalings cooperatively contribute to liver regeneration and could provide new insights into tissue homeostasis."
18068850
reach
"In vitro cell experiments indicated that overexpression of EGFR activated the JAK2/STAT3 signaling pathway and reduced neuronal apoptosis levels."
37656314
reach
"Blockade of uPAR and MMP9 Inhibited EGFR Mediated Activation of STAT3."
22984561
reach
"Moreover, mutations in EGFR kinase domain have been shown to mediate STAT3 activation by IL-6 production in human lung carcinomas (Gao et al, 2007), suggesting that EGFR like STAT3 activation can be mediated by IL-6R or GP130 receptors in an autocrine manner."
19088723
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"Of which, the EGFR and HER2 can activate STAT3 via phosphorylation through SRC to promote cell survival ( xref )."
36689784
reach
"The few reports with respect to the ability of EGFR versus EGFRvIII to activate STAT3 in GBM have shown rather inconsistent results."
20030624
sparser
"Also, further targets of the transcriptionally active heterodimer EGFRvIII/STAT5 are needed to be identified, it is clear that both EGFRvIII-activated STAT3 and STAT5 are involved in the induction of [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
28583430
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"STAP-2 upregulates EGFR-mediated signaling, enhancing STAT3 activity in DU145 prostate cancer cells [8]."
38745775
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"EGFR stabilization by STAP-2 further enhances EGFR signaling and STAT3 upregulation."
38745775
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"IL6 was consistently and significantly increased by EGFR TKI treatment in two distinct EGFR-mutant NSCLC model (XREF_FIG), and was recently implicated as a mediator of EGFR TKI induced STAT3 activation."
25843712
reach
"Reduction of EGFR activation decreased STAT3 activation, which could attenuate the development of fibrotic progress."
26550019
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"As IL6 promotes JAK2 and STAT3 activation, we hypothesized that NF-kappaB may be required for EGFR TKI induced STAT3 activation."
25843712
sparser
"Endosomal STAT3 activation by EGFR and HGFR/MET is further enhanced through the recruitment of the cytoplasmic tyrosine kinase PYK2 to early endosomes, representing a positive feedback loop to sustain endosomal STAT3 activation and to promote epithelial-to-mesenchymal transition (EMT) and therefore tumor invasiveness ( xref )."
34141712
reach
"As epidermal growth factor receptor (EGFR)-mediated activation of Erk, STAT3, and PI3K/Akt signaling are necessary for EMT regulation, whether BBR acts on these key active proteins was determined in silico using a molecular docking analysis."
36308362
reach
"In the presence of alectinib, HGF or EGFR ligands restored AKT and ERK1/2, but not STAT3, phosphorylation and thereby made EML4-ALK cells insensitive to alectinib."
24952482
sparser
"Since STAT3 is activated by EGFR and IL-6R, EGFR inhibition in combination with IL-6 antagonists [ xref ] or STAT decoy oligonucleotides [ xref ] holds potential for synergistic activity."
19570715
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"Multiple signaling pathways converge on STAT3 activation, such as IL-6 and JAKs, EGFR, Src, and is overexpressed in a variety of tumor cells and tissues."
28223148
sparser
"STAT3 has also been linked to EGFR signaling, where EGFR can activate STAT3 and it complexes with mutant, activated forms of EGFR-vIII to drive tumorigenesis xref ."
29777182
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"The Ang II/I receptor axis activates NF-кB, which generates epidermal growth factor receptor ligands and TNF-α, which also stimulates NF-кB. Signal transducer and activator of transcription 3 (STAT3) is required to fully activate the NF-кB pathway, and the main stimulator of STAT3 is IL-6."
34966658
sparser
"Previous reports have shown that the EGFR kinase directly activates STAT3 [ xref ], and that is likely the case in the MDA-MB-468 and A431 cells, particularly based on the kinetics of STAT3 phosphorylation."
28433699
reach
"Whereas EGFR can stimulate NFnB and STAT3, recent observations indi-cate that HNSCC can also exhibit EGFR independent acti vation of these key signaling routes [13]."
16984731
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"Bioassay guided isolation of cantharidin from blister beetles and its anticancer activity through inhibition of epidermal growth factor receptor mediated STAT3 and Akt pathways."
30043217
reach
"Epidermal growth factor receptor (EGFR), which senses the EGF ligand, activates downstream Akt and STAT3 pathways to promote metastasis in prostate cancer [142] ."
38643904
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"Altogether, the molecular mechanism underlying UA 's anticancer activity depends on EGFR signaling, which then signals to JAK2 and STAT3, causing STAT3 to translocate to the nucleus to bind with the VEGF, MMP2, and PD-L1 promoters in order to block their transcription, thus inhibiting tumor angiogenesis, invasion, metastasis, and tumorsphere formation (XREF_FIG)."
| PMC
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"SRIURANPONG V, PARK JI, AMORNPHIMOLTHAM P et al. : Epidermal growth factor receptor independent constitutive activation of STAT3 in head and neck squamous cell carcinoma is mediated by the autocrine and paracrine stimulation of the interleukin 6/gp130 cytokine system."
15469392
sparser
"The overexpression of ErbB2 and ErbB3 selectively activated STAT5a (Fig.  xref ), similar to ErbB4 JM-a, while EGFR activated STAT5b and STAT3 (Fig.  xref ), similar to ErbB4 JM-b."
36376313
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"XREF_BIBR, XREF_BIBR The observations herein would be consistent with the Gef-NArg conjugates preventing EGFR mediated STAT3 activation, while both molecules are in the nucleus, but a more complete mechanistic understanding would require further studies."
28787571
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"EGF receptor and PDGF receptor can directly activate STAT3 (Ruff-Jamison et al., 1994; Liu et al., 2023a)."
38495094
reach
"More recently, it has been shown that in a subset of glioblastomas the EGFR driven activation of STAT3 requires : a. the phosphorylation of EGFRvIII by EFGR, b. the nuclear entrance of EGFRvIII, and b. the formation of an EGFRvIII and STAT3 complex in the nucleus [XREF_BIBR]."
25885672
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"As STAT3 is activated by EGFR [XREF_BIBR], we examined whether EGFR is involved in gemcitabine enhanced invasion by activating STAT3."
27556697
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"EGFR expressing cells enhances the activity of STAT3."
23359207
sparser
"For instance, EGFR-dependent STAT3 activation requires the association of the IL-6 receptor and gp130 with EGFR [ xref ]."
39885395
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"As shown above, HAb18G and CD147 and EGFR activate STAT3 signaling, contributing to gemcitabine enhanced invasion."
27556697
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"EGFR with constitutively active mutations leads to the continuous activation of the STAT3 pathway [41]."
38534309
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"As the CD147 activation and knock-down influenced the pEGFR levels accordingly, EGFR activated pSTAT3 signaling depended on HAb18G and CD147 levels."
27556697
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"Here we present evidence that both exogenous IGFBP2 treatment and cellular IGFBP2 overexpression lead to aberrant activation of EGFR, which subsequently activates STAT3 signaling."
25893308
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"Furthermore, we demonstrate that IGFBP2 augments the nuclear accumulation of EGFR to potentiate STAT3 transactivation activities, via activation of the nuclear EGFR signaling pathway."
25893308
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"It should be noted that in addition to JAK, STAT3 activation can also be mediated by the Src family, Abl family, EGFR, and insulin-like growth factor-1 receptor (IGF-1R) (63)."
38192990
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"PI3 K/AKT, MAPK/ERK, and STAT3 are all activated by EGFR activation, and these pathways together result in angiogenesis, invasion, proliferation, and an inflammatory response—all of which are characteristics of cancer [48]."
40299087
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"Stat3 activation by the EGFR has been mapped to the COOH-terminal region of the EGFR between amino acid residues 1061 and 1123, which contains Y1068 and Y1086."
12873986
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"EGFR is known to activate and maintain STAT3 signaling, driving transcriptome rewiring events that promote cancer progression and drug resistance [XREF_BIBR]."
31288129
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"We observed STAT3 phosphorylation in these cells, confirming that EGFR knockdown impairs STAT3 activation by IGFBP2 without compromising alternate STAT3 activation pathways (XREF_SUPPLEMENTARY)."
25893308
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"In contrast, we could not observe a significant difference in STAT3 signalling mediated by wild-type leptin in LR or LR + EGFR transfected cells (Fig. 2c)."
30659329
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"Src mediated EGFR transactivation is not required for Akt activation triggered by T. gondii but mediates ROP16 independent STAT3 activation."
29036202
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"STAT3 is robustly activated by EGFR, and this activation is sustained due to strong positive feedback from STAT3 to EGFR (Figure 5A)."
39001416
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"In this study, we demonstrated in stably transfected NIH-3T3 cells that activation of Stat3 by EGFR was eliminated by mutation of all five EGFR tyrosines to phenylalanine and that activation was restored with return of two of the mutated tyrosine sites, Y1068 and Y1086, to wild-type."
12873986
sparser
"In HNSCC, activation of STAT3 by IL-6 and EGFR has been proven to be a key molecular event [ xref , xref ]."
27174914
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"Thus, we examined whether Src and EGFR Y845 mediate rapid STAT3 activation in T. gondii infected cells."
29036202
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"To examine whether EGFR Y845 phosphorylation promotes STAT3 activation triggered by T. gondii, human epithelial cells were transfected with a plasmid encoding WT EGFR or Y845F EGFR."
29036202
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"Studies show that cell transformation during EMT may be caused by direct or indirect (mediated via EGFR - epidermal growth factor receptor) activation of transcription factor STAT3 by fibronectin [ 43[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
34023767
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"Most pertinent to this review, epidermal growth factor (EGFR) activation of STAT3 [94] , TGFβ [31,95] , and Epb1 activity [96] can increase PDPN expression in cancers including OSCC.PDPN contains an a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29496040
reach
"Phosphorylation of EGFR also induces the activation of signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathways [15]."
37029114
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"Furthermore, co-expression of EGFR partially restores STAT3-dependent signalling by this mutant through the LR (Fig. 2b)."
30659329
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"In human lung adenocarcinoma, mutations in the EGFR kinase domain mediate signal transducer and activator of transcription 3 (STAT3) activation through interleukin (IL)-6 production (17)."
36815969
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"In addition, ADAM17 also promotes STAT3 activation by induction of EGFR/IL-6 transduction signaling pathways, which ultimately lead to tumor progression; inhibition of the ADAM17/IL-6/STAT3 signaling axis significantly attenuated the growth of colon cancer cells (210)."
36466812
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"However, the overexpression of the JAK family by the SOCS antagonist, and enhanced EGFR signalling that activates STAT3 during the late infection stage may contribute somewhat towards the cytokine storm, the main contributor to ARDS which maybe life‐threatening."
34546610
reach
"In epithelial tumors, STAT3 activation is mediated by EGFR, erythropoietin receptor, IL-6 receptor, PDGFR, c-Met, and IGF1R."
19223541
sparser
"STAT3 is activated by receptor tyrosine kinases EGFR, HER2, fibroblast growth factor receptor (FGFR), IGFR, HGFR and platelet-derived growth factor receptor (PDGFR), receptor-associated kinases (JAK) and non-receptor kinases (Src and Abl) through phosphorylation [ xref , xref ]."
24743778
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"Epidermal growth factor receptor - independent con-stitutive activation of STAT3 in head and neck squamous cell carcinoma is mediated by the autocrine and paracrine stimulation of the interleukin 6/gp[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16984731
reach
"In tumor cells, interleukin-6 (IL-6) signaling can lead to activation of the epidermal growth factor receptor (EGFR), which prolongs Stat3 activation."
39000275
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"Furthermore, we showed that ALYREF stabilized EGFR by binding to the m5C site of EGFR mRNA, which in turn activated the STAT3 signaling pathway and consequently enhanced LIHC progression, suggesting an m5C-dependent oncogenic role of ALYREF towards LIHC.Our findings have extended the regulatory mechanism of ALYREF expression from an epigenetic perspective and revealed a new mechanism for regulating EGFR expression through m5C modification, indicating that ALYREF-induced m5C epigenetic regulation may have therapeutic benefits in LIHC."
38164181
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"Taken together, this study provides evidence that cantharidin may be a potential therapeutic agent for triple negative breast cancer by reducing EGFR mediated STAT3 and Akt signaling pathways."
30043217
reach
"EGFR mediates the activation of Janus kinase/signal transducer and activator of transcription 3 (STAT3) (Ueno et al, 1997); AKT, involved in cell survival; and ERK1/2, which regulates cell stress and proliferation (Meloche & Pouysségur, 2007; Lill & Sever, 2012; Goffin & Zbuk, 2013)."
38977310
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"In this case, the signal from hTERT to STAT3 can be transduced by the previously mentioned EGFR, which phosphorylates and thereby activates STAT3 [XREF_BIBR]."
22872811
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"The relationship between LIF- and EGFR induced STAT3 activation is also found in various types of cells, such as lung carcinoma cells [XREF_BIBR] and ovarian cancer cell lines [XREF_BIBR]."
27096934
sparser
"Since EGFR and IL-6 activate STAT3, STAT decoy oligonucleotides can be used in synergism with EGFR or IL-6 antagonists. xref "
36683526
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"This, in a secondary process, leads to binding of EGFR to the IL-6 receptor and prolongation of Stat3 activity at high levels, mediated by EGFR stimulation [23]."
39000275
sparser
"In vitro studies in primary MECs and transfected COS-7 cells showed p44/42 MAPK and EGFR-dependent STAT3 activation."
30448440
sparser
"Park OK, Schaffer TS, Nathans D. In vitro activation of Stat3 by epidermal growth factor receptor kinase."
10757107
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"Colomiere et al. [36] indicated that EGFR-induced crosstalk with the IL-6R pathway may result in the acquisition of some EMT-associated phenotypes in ovarian cancer, although emphasis was placed on EGFR-mediated STAT3 activation, and the evidence for IL-6-induced EMT was incomplete.Hypoxia is a factor of the microenvironment in almost all tumor types and is known to upregulate multiple mediators and pathways that induce tumor EMT [37]."
36814597
sparser
"Moreover, the EGFR activates STAT3 in lung cancer cell lines xref and can promote tumor survival in vivo in NSCLC by signaling through STAT3 xref ."
25926075
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"FIP200 depletion results in reduced phosphorylation of epidermal growth factor receptor (EGFR), decreased STAT3 activation and consequently impairs the tumourigenic potential of ALDH breast CSCs (Ref."
39375840
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"EGFR may activate the aerobic glycolysis pathway in iCCA cells by activating the STAT3 signaling pathway."
35851575
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"Butaprost also induced the activation of AKT, ERK1/2, and STAT3, all of which were inhibited by beta-arrestin deficiency or EGFR inhibition."
22012553
reach
"Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas."
23134344
sparser
"As we had previously shown that sustained Stat3 activation results in the desensitization of TGF-β signaling in the IL-6/gp130 signaling system, xref we next set out to determine whether EGFR activated Stat3 in several human cell lines."
22751114
sparser
"We identified Stat3, which is activated specifically and persistently by overexpressed EGFR, as a key signaling molecule responsible for the reduced TGF-β sensitivity."
22751114
reach
"The phosphorylation of these dimerized receptors occurs reciprocally, with VEGFR inducing JAK2 phosphorylation and EGFR inducing c-Src kinase phosphorylation, thereby facilitating the activation of the STAT3 pathway [123]."
38920657
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"Constitutively activated mutant variants of EGFR can promote IL-6 production and activate JAK/STAT3 signaling pathway in human lung adenocarcinomas."
24076269
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"Genetic alterations at 17p13 (encoding p53) and 9p21 (encoding p14 and p16) have been reported in HNSCC and both epidermal growth factor receptor (EGFR)/signal transducer and activator of transcription 3 (STAT3) and PI3 kinase/PTEN/Akt pathways are activated in HNSCC."
20676130
sparser
"Both Ras and STAT3 proteins are activated by EGFR [ xref , xref , xref ] and suppressed by the microRNA let-7 [ xref , xref , xref , xref ], and both of them regulate the common downstream targets, such as cyclin D1 [ xref , xref , xref ], Bcl2 family proteins [ xref , xref , xref , xref ], Rho family GTPases [ xref , xref , xref ], hypoxia-inducible factor-1α [ xref , xref ], and VEGF [ xref , xref ], suggesting that Ras and STAT3 mediate certain parallel, complementary, or coordinated biological processes ( xref )."
24662938
reach
"Interestingly, EGFR activation can result in Src/FAK/BTK mediated activation of STAT3, thereby modulating the IFN and proinflammatory responses."
36968089
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"Minocycline effectively inhibits activation of EGFR driven STAT-3 in U373 GBM cells at a concentration of 100muM [XREF_BIBR]."
33014057
reach
"These gain and loss of function of EGFR results demonstrate that EGFR is a significant activator of STAT3 in MPNST cells."
23318430
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"Through upregulating the expression and nuclear trafficking of EGFR, STEAP3 participated in regulating EGFR-mediated STAT3 transactivity in a manner of positive feedback."
34741044
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"Minocycline has been proposed to have several anticancer mechanisms of action in GBM, including inhibition of proinflammatory and metastatic enzymes, such as iNOS and MT1-MMP signaling functions, GFAP, COX-2, NF-kappaB, IL-1beta, and TNF-alpha downregulation, autophagic cell death induction, caspase-3 activation, suppression of microglia activation, inhibition of M1 microglia polarization, p38 MAPK inhibition, inhibition of EGFR driven STAT-3 activation, and targeting the TLR2 signaling pathway."
33014057
sparser
"In addition, EGFR also activates STAT3 in a JAK-independent mechanism [ xref ]."
32967366
sparser
"Our observation that the tumor-associated overexpressed EGFR activates Stat3 persistently identifies EGFR as a physiologically relevant upstream molecular cause of Stat3 activation."
22751114
sparser
"These indirubin derivates have not been tested in SCC cells so far, but since EGFR, which activates STAT3, is frequently overexpressed in SCC ( xref ), targeting STAT3 may provide a promising approach for SCC treatment as well."
| PMC
reach
"In addition to IL-6 signaling, STAT3 can be activated by EGFR, PDGFR, and Src kinase."
24101903
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"It was reported that, in head and neck cancer cells in which activation of STAT3 by epidermal growth factor receptor (EGFR) protects against apoptosis, abrogation of STAT3 activity markedly enhanced c[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23402820
sparser
"In a recent publication in Nature Communications , Bi and colleagues demonstrated the importance of TMEM25 (transmembrane protein 25) in the regulation of epidermal growth factor receptor (EGFR)‐dependent STAT3 (signal transducer and activator of transcription 3) activation in triple‐negative breast cancer (TNBC)."
38532948
sparser
"They proved that lack of TMEM25 enables monomeric EGFR to activate STAT3 in a ligand‐independent fashion in preclinical TNBC models, suggesting the importance of blocking the monomeric EGFR/STAT3 signaling axis in TNBC. xref TNBC represents one of the aggressive types of breast cancer, and it accounts for approximately 15% of total breast cancers."
38532948
reach
"In cancer, HCK activation interacts with receptor tyrosine kinases (RTK), such as platelet-derived growth factor receptor (PGDFR), epidermal growth factor receptor (EGFR), and fibroblast growth factor receptor (FGFR), activating ERK, AKT, and STAT3 signaling pathways, further stimulating cell proliferation [14]."
32484210
reach
"In addition, EGFR can directly activate STAT3 or through Src and JAK–STAT3, which can then dimerize and translocate into nucleus, where it can promote cell differentiation, survival, and proliferation (15)."
38536914
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"This interaction triggered EGFR-mediated STAT3 activation, leading to ICAM-1 upregulation and induction of EMT in breast cancer cells."
39415210
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"Interestingly, EGF receptor (EGFR) signaling contributes to tumor progression in the mouse AOM model 46, and the ability of EGFR to activate STAT3 signaling would be impaired in the Ptk6 -/- mice."
21741923
reach
"Interestingly, EGF receptor (EGFR) signaling contributes to tumor progression in the mouse AOM model 46, and the ability of EGFR to activate STAT3 signaling would be impaired in the Ptk6 -/- mice."
21741923
reach
"STAT3 can be activated by EGFR or IL-6."
28032598
sparser
"Mechanistically, a lot of tumor- and TME-derived signals, such as hypoxia, EGFR-induced STAT3 and NF-κB activation, might be responsible for upregulated NEAT1 expression."
32843056
reach
"Additionally, EGFR independent activation of STAT3 through cytokine stimulation promoted apoptosis, as measured by PARP and Caspase-3 cleavage."
28433699
sparser
"The current study suggests that the EGFR-induced activation of STAT3 is more complicated than thought previously."
15950906
sparser
"Here, we show that EGFR-dependent STAT3 activation is restricted to malignant keratinocytes."
15173005
reach
"Since the SFK and JAK pathways selectively regulate EGF mediated vimentin induction, we sought to further characterize the regulation of vimentin induction downstream of EGFR stimulation in MDA-MB-468[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
27163529
reach
"Previous studies have shown that STAT3 can be activated by both EGFR dependent and -independent pathways and that STAT3 inhibition can result in tumor growth inhibition and/or apoptosis [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."
33809148
reach
"ICAM-1 directly interacts with EGFR, activating the EGFR-mediated STAT3 pathway and inducing epithelial-mesenchymal transition (EMT)."
39415210
reach
"DR1-CSE/H2S pathway activation inhibits the proliferation of MOVAS in HG-induced by down-regulating IGF-1/IGF-1R, HB-EGF/EGFR as well as their downstream PI3K/Akt, JAK2/STAT3 and ERK1/2 pathways."
35656112
reach
"STAT3 can be also activated by EGFR, JAK2, and other tyrosine kinases activated by EGF, leukemia inhibitory factor (LIF), and other cytokines."
23838182
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"The abundance of STAT3 in the particulate compartment (presumably representing nuclear localization) in early pregnancy makes perfect sense since STAT3 is activated by EGF-R which, as noted earlier, i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
11728516
sparser
"In addition to the traditional pathway in which EGFR activates STAT3 and activated STAT3, in turn, translocates into the nucleus to turn on gene expression, another mode of regulation could be derived[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
15950906
reach
"We provided evidence of a novel link among NADPH oxidase and Stat3 signaling, mediated by Src, EGFR, and Erk1/2."
23376140
sparser
"As STAT3 is activated by EGFR [ xref ], we examined whether EGFR is involved in gemcitabine-enhanced invasion by activating STAT3."
27556697
reach
"To examine whether IL-6 and EGFR activate STAT3 in podocytes, we blocked IL-6 and EGFR in cultured primary podocytes and performed western blotting to determine STAT3 phosphorylation (Tyr705), which is a marker of STAT3 activation."
29184126
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"In vitro activation of Stat3 by epidermal growth factor receptor kinase."
9442382
reach
"Mechanically, increased nuclear STEAP3 expression significantly promoted the stemness phenotype, cell cycle progression, and cellular proliferation of HCC cells, through RAC1-ERK-STAT3 and RAC1-JNK-STAT6 signaling axes, while STEAP3 also upregulated the expression and nuclear trafficking of epidermal growth factor receptor (EGFR) to promote EGFR-mediated STAT3 transcription activity in a positive feedback manner[101]."
38292664
reach
"EGFRvIII increases STAT3 activation."
20622897
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"To determine whether STAT3 is differentially activated by EGFRvIII, we analyzed expression of tyrosine phosphorylated STAT3 by immunoblotting in addition to STAT3 transcriptional activity in the EGFRvIII expressing HNSCC cells compared with vector-controls."
20622897
reach
"In recent years, tremendous efforts have been made toward developing allosteric inhibitors targeting various members of the STAT3 signaling pathway.Cell surface receptors, including EGFR, FGFR, VEGFR,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32066011
reach
"To determine the effects of cetuximab on EGFRvIII mediated STAT3 activation, HNSCC cells expressing EGFRvIII were treated with cetuximab followed by STAT3 promoter assays."
20622897
reach
"Previous reports have shown that the EGFR kinase directly activates STAT3 [XREF_BIBR], and that is likely the case in the MDA-MB-468 and A431 cells, particularly based on the kinetics of STAT3 phosphorylation."
28433699
reach
"C-MET and EGFR family function independently to promote STAT3 activation, thereby sustaining the proliferation of drug-resistant cells."
34348188
reach
"These results suggest that EGFR and EGFRvIII driven STAT3 activation depends on TRIM24 linked histone modification."
29129908
reach
"Aberrant EGFR signaling in GBM mediates STAT3 transcriptional activation to promote tumorigenesis, progression and invasion of glioblastoma XREF_BIBR, XREF_BIBR."
29129908
reach
"Although a large body of knowledge has established the mechanisms by which EGFR activates STAT3 through JAK or Src 48, in this study, we show a novel mechanism by which activated EGFR enhances H3K23 acetylation and TRIM24 expression, promoting the association of TRIM24 with H3K23ac and STAT3, and facilitating STAT3 interaction with chromatin, leading to downstream signaling activation to drive glioma tumorigenesis."
29129908
reach
"ROS produced by this oxidase activates Src, enable that in turn, transactivates EGFR that activates Stat3 in tyrosine, allowing its dimerization."
23376140
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"These results suggest that EGFR and EGFRvIII driven STAT3 activation depends on TRIM24 linked histone modification."
29129908
sparser
"Here, we show that STAT3 is activated by mutant EGFRs and is necessary for its downstream phenotypic effects."
16540667
sparser
"In addition, EGFR can directly activate STAT3 or through Src and JAK–STAT3, which can then dimerize and translocate into nucleus, where it can promote cell differentiation, survival, and proliferation ( xref )."
38536914
reach
"TGFbeta and/or EGF and EGFR mediated STAT3 activation also has been observed to possess a pivotal role in EMT through increased TWIST1 expression in MC cells [XREF_BIBR], [XREF_BIBR]."
25266665
reach
"EGFR overexpression further activates STAT-3 and increases lung pathology."
34806405
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"Using HaCaT keratinocytes, knockdown of Dsg2 decreases EGFR expression and abrogates the activation of EGFR, c-Src and Stat3, but not Erk1/2 or Akt, in response to EGF ligand stimulation."
26918609
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"These findings suggest that DR1 activation increases endogenous H S production, which inhibits HG-induced VSMCs proliferation by down-regulating IGF-1/IGF-1R and HB-EGF/EGFR, as well as their downstream PI3K/Akt, JAK2/STAT3 and ERK1/2 pathways.The above experimental results confirmed that DR1 activation inhibits VSMCs proliferation by increasing endogenous H S production in T1MD mice and HG-induced VSMCs."
35656112
reach
"Mutation in EGFR (Epidermal growth factor receptor), FGFR3b (Fibroblast growth factor receptor), H-ras and NOTCH1, upregulated activation of c-Met, STAT3, NF-κB, AP-1 stimulates OSCC cell proliferatio[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35671689
reach
"EGFR overexpression further activates STAT-3 and increases lung pathology [2,5–8]."
34806405
reach
"Mechanistically, a lot of tumor- and TME derived signals, such as hypoxia, EGFR induced STAT3 and NF-kappaB activation, might be responsible for upregulated NEAT1 expression."
32843056
reach
"EGFR induced STAT3 activity has a well established role in the growth of primary human tumors that express high levels of EGFR including TNBC."
28088463
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"We therefore hypothesize that perhaps EGFR mediated STAT3 activation kinetics differ from those of IL-6 to account for their differential effect on proteasome subunit induction."
27132469
reach
"Here, we provide evidence that Pyk2, along with c-Src, facilitates EGFR mediated Stat3 activation."
14963038
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"Based on results from specific inhibitor assays (AG14789 and PD168393), the EGFR pathway also appears to contribute to and enhance STAT3 activation."
17961551
sparser
"STAT3 is also activated by Src kinase, ABL and EGFR [36] ."
26612419
reach
"STAT3 can be activated by phosphorylation of EGFR, JAK, Src, and other classical tyrosine kinases, and it is the junction of multiple carcinogenic tyrosine kinase signal channels."
38144543
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"These findings together suggest the EGFR and Src kinase activities promote the association of Stat3 with EGFR in the nuclear heteromeric complex, while the inhibition of EGFR or Src kinase alone does not preclude the interaction between EGFR and Src."
21573184
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"Present data also suggest that only a portion of the intracellular EGFR, Src and Stat3 protein pools are utilized in the formation of the nuclear complex, raising the possibility that there may be diverse cellular pools of EGFR, Src, or Stat3 with different accessibility limitations."
21573184
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"ErbB-2, another EGFR family receptor kinase, has been shown to activate STAT3 in an Src and JAK2 dependent manner [43]."
17961551
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"In addition, p-STAT3 expression has been positively correlated to cyclin D1 expression, while the activation of epidermal growth factor receptor in glioma cells can cause excessive activation of STAT3, and the resulting increased expression of cyclin D1 drives the accelerated proliferation of tumor cells."
29551899
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"In conclusion, our findings identify TRIM24 as an oncogenic transcriptional co-activator in EGFR driven GBM and also demonstrate a previously unknown signal relay by which H3K23ac and TRIM24 mediates EGFR stimulation of STAT3 activation, thereby enhancing the oncogenic activity of the EGFR and STAT3 pathway in human cancers."
29129908
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"Our data reveal that in basal conditions expression of 247R genetic variant of alpha 1a AR leads to STAT3 activation that is inhibited by EGFR- and MMP- specific inhibitors, demonstrating EGFR transactivation dependent STAT3 activation."
24835978
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"XREF_BIBR, XREF_BIBR EGFR activation results in downstream STAT3 activation in a JAK dependent manner, presumably through FGFR and IL-6 signaling."
27613527
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"Although VEGF and EGFR can activate JAK and STAT3 signaling pathway, a variety of extracellular stimuli especially IL6 expression, is necessary for the activation of STAT3 signaling [XREF_BIBR - XREF_BIBR]."
27729020
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"An example of STAT activation independently of JAK is the activation of STAT3 by epidermal growth factor receptor (EGFR) most notably by c-Src XREF_BIBR, XREF_BIBR."
24416369
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"EGFR activated STAT3, for example, is critical for lung cancer metastasis (Soon, Leong, Koh, & Tham, 2015)."
33304472
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"EGFR is also known to activate STAT-3 and thus its downstream target genes involved in cell proliferation and survival (such as c-Myc and survivin)."
23762292
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"While inhibition of Src or EGFR signaling pathways temporarily reduces constitutive STAT3 in pancreatic cancer cell lines, reactivation of STAT3 occurs rapidly XREF_BIBR, XREF_BIBR."
24015205
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"EGFR overactivation may result in the resistance of tumor cells to chemotherapy and radiation treatment, via the activation of the PI3K/Akt, JAK/STAT3 and Ras/Raf/MEK/Erk downstream signaling pathways [41]."
30947731
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"Additionally, as discussed above, EGFR signaling induced by E-cadherin-mediated intercellular adhesion could initiate and modulate STAT3 activation through autocrine and paracrine mechanism [44]."
17961551
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"Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas."
18060032
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"The STAT3 signaling pathway mediated by EGFR and Src is activated in tamoxifen-resistant luminal-type cells."
39468521
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"A previous study by Li et al (102) found that, in triple-negative BC, knockdown of NCAPG resulted in a significant decrease in the expression of p-EGFR, p-JAK1 and p-STAT3, although the inhibitory effect of knockdown of NCAPG on p-STAT3 could be reversed by using agonists of the EGFR and JAK/STAT3 signalling pathways, accompanied by an increase in cell proliferation, invasion and migration and a decrease in apoptosis."
38639175
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"13 However, mutations in the EGFR kinase domain (p.T790M) could activate the STAT3 pathway via an increase in IL-6 levels."
39735443
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"STAT3 may work as a downstream of EGFR signaling pathway and EGFR can activate STAT3 pathway from several aspects."
33391507
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"STAT3 is activated by EGFR signaling and is a key molecule in maintaining skin homeostasis."
36530656
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"The aberrant expression of EGFRvIII regulates cancer progression [25] and modulates STAT3 signaling [26,27], which is involved in the control of cell stemness [28]."
40003899
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"The reduction of STAT1 or acute lung injury also upregulates epidermal growth factor receptor (EGFR), further enhancing STAT3 activity [63], [64]."
34687900
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"Like HER2, abnormal EGFR activity has been shown to enhance STAT3 activation, which leads to tumor start, growth, and metastasis."
39493231
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"Dual SFK-EGFR targeting could overcome cetuximab resistance by inhibiting EGFR independent activation of STAT3 by Src."
28559019
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"An example of STAT activation independently of JAK is the activation of STAT3 by epidermal growth factor receptor (EGFR) most notably by c-Src xref , xref ."
24416369
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"SFK- and EGFR independent activation of pSTAT3 through increased IL6 is one possible explanation for this finding."
28559019
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"Epidermal growth factor receptor mediated activation of Stat3 during multistage skin carcinogenesis."
19466902
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"Our results showed that AL enhanced the expression of AQP3 and HAS2 by activating the EGFR-mediated STAT3 and MAPK signaling pathways."
37047782
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"EGFR Promotes the Development of Triple Negative Breast Cancer Through JAK/STAT3 Signaling."
32099467
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"The first evidence of an interrelation between the EGFR and IL-6 pathway was revealed by Gao et al. [74] when they demonstrated that mutations in the EGFR kinase domain activate the STAT3 pathway via [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29680500
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"Sun et al. revealed that the EGFR T790M-cis-L792F induced the JAK/STAT3 pathway, promoting p-STAT3 (Tyr705) to bind specifically to the IL-4 promoter."
38341519
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"EGFR Promotes the Proliferation and Invasion of Cancer Cells Through p-STAT3."
32099467
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"Yu et al. showed that mTOR activation [as indicated by phosphorylated substrate-S6 (p-S6) overexpression] promotes angiogenesis in ACC through the Epidermal growth factor receptor (EGFR)/Signal transducer and activator of transcription-3 protein (p-Stat3) and Hypoxia inducible factor-1alpha (HIF-1alpha)/Plasminogen activator inhibitor (PAI) pathways (activation of EGFR results in activation of Stat-3 and HIF-1a induces PAI production)."
33302367
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"Mechanistically, EpEX induced an EGFR-dependent STAT3 activation and the blockade of Let7 microRNA through upregulation of LIN28 [ xref ]."
32507912
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"STAT3 can be activated by EGFR, JAK2, and other tyrosine kinases whose activation can be mediated by EGF, leukemia inhibitory factor (LIF), and other cytokines."
18829483
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"Furthermore, continuous EGFR signalling from late endosomes contributes to sustained downstream AKT and STAT3 but not ERK1/2 or p38 signalling cascades."
27387133
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"EGFR Activates JAK/STAT3 Signaling."
32099467
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"The results of in vivo experiments suggest that EGFR-mediated STAT3 activation plays an important role during the tumor promotion stage of skin carcinogenesis induced by tumor initiator 7, 12-dimethyl[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18995957
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"In colon cancer cells, where EGFR is a major mediator of carcinogenesis, this negative regulation was overcome by co-association of IL-6, IL-6R and EGFR into a complex in which JAK mediated phosphoryl[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29680500
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"EGFR-Activated JAK2/STAT3 Pathway Confers Neuroprotection in Spinal Cord Ischemia-Reperfusion Injury: Evidence from High-Throughput Sequencing and Experimental Models."
37656314
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"In the present study, we further confirmed that STAT3 could be activated by EGFRvIII, and inhibition of STAT3 activation or knock down of STAT3 could inhibit S100A11 expression and S100A11 promoter activity."
24376686
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"It has been suggested that JAK-dependent or -independent STAT3 is possibly involved in EGFR-mediated STAT3 pathway."
18995957
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"Notably, only EGFR TKIs or EGFR knockdown by siRNA increased pStat3, indicating that Stat3 activation is specific for EGFR inhibition in these EGFR addicted cells, regardless of the induction of apopt[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25065853
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"Upon activation, EGFR undergoes dimerization and endocytosis, during which EGFR upregulates AKT1, STAT3 and RAS signaling pathways to promote DNA synthesis and cell proliferation [36] ."
28428083
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"It has been reported that Bcl-xL is regulated by EGFR-activated STAT3 to promote survival in head and neck cancer xref ."
24621885
sparser
"As a direct transcription factor, STAT3 is activated by EGFR, phosphorylated by JAK2, and translocates to the nucleus as dimers."
36933872
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"Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas [277] ."
24552665
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"It is worth noting that aberrant activation of STAT3 by other factors such as IL-6 and epidermal growth factor receptor (EGFR) is also correlated with lung carcinogenesis [ 78–80 ]."
33612289
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"In addition, EGFR signaling has been shown to activate signal transducer and activator of transcription proteins (STAT) XREF_BIBR, particularly STAT3 mediated signaling XREF_BIBR."
23620784
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"Carnosol, luteolin and cirsiliol showed dose-dependent anti-proliferative activity against hepatoma HepG2 cells and lung cancer A549 cells and their anti-proliferative activity was enhanced by gefitinib, which is known to inhibit EGFR-dependent STAT3 activation but not IL-6-dependent STAT3 activation [ xref ] ( xref A and B)."
33392396
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"We have previously shown that in the GBM cell line U87, Stat3 is activated by EGFR and that activated Stat3 suppresses the spontaneous apoptosis of U87 cells by upregulating the expression of the pro survival protein Mcl-1 in vitro."
19121577
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"Although the compounds reported as STAT3 signal inhibitory compounds [ xref , xref , xref ], cirsiliol inhibited IL-6-dependent STAT3 reporter expression only in a partial manner since cirsiliol did not dose-dependently inhibit reporter expression beyond 30 μM ( xref C and D), prompted us to compare the effect of these compounds on STAT3 protein with or without phosphorylation and the additive anti-proliferative effect to that of gefitinib which inhibits EGFR-dependent STAT3 activation."
33392396
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"Our studies show that poultry dust extract controls the induction of immune and inflammatory mediator levels via a cellular pathway involving oxidative stress mediated STAT-3 activation by Tyk2 and EGFR tyrosine kinases."
31042082
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"EGFR can activate STAT-3 [ xref ]."
39290346
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"Since EGFR induced STAT3 activation has been shown to promote resistance to proteasome inhibitors in MM cells [XREF_BIBR], we asked if the STAT3 activation in MM-3D cells contributes to resistance to bortezomib, a proteasome inhibitor commonly used in treating MM patients."
29914181
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"STAT3 shRNA can reduce specific and sustained EGFR-dependent activation of STAT3 in the HN5 head and neck tumor cell line [160]."
38067351
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"Hypoxic conditions upregulate EGFR expression which, activating downstream pathways (ERK1/2 and STAT3) that induce the secretion of the antiangiogenic soluble FMS-like tyrosine kinase-1 (sFlt-1) from the placenta."
39966897
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"Park OK, Schaefer TS, Nathans D : In vitro activation of STAT3 by epidermal growth factor receptor kinase."
9382798
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"Since STAT3 is activated by EGFR [XREF_BIBR], it further explains the observed decrease in both EGFR and STAT3 in BCC cells in response to silibinin and DHS treatments."
25492239
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"STAT3 is activated by receptor (epidermal growth factor receptor (EGFR), kinase insert domain receptor (KDR), hepatocyte growth factor receptor (MET)) or non receptor (janus-kinase (JAK), SRC) tyrosine kinases mediated phosphorylation at Y705."
32442087
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"In this study, we show that a reduction in plasma membrane-associated EGFR triggers EGFR transcription by promoting pSTAT3 nuclear localization."
39967270
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"AG1478, an inhibitor of the EGFR, downregulated Stat3 activation in HSC-1 human SCC cells."
21197106
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"Erlotinib, an EGFR-targeted tyrosine kinase inhibitor (TKI) used to treat NSCLC patients, can activate STAT3 signaling [28]."
39967270
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"In response to irradiation, EGFR also functions anti-apoptotically, especially in heterodimers with ERBB2 [XREF_BIBR], and transcriptionally activates anti-apoptotic BCL2L1 via SRC and STAT3 (signal transducer and activator of transcription 3) signaling [XREF_BIBR]."
26784176
sparser
"The epidermal growth factor receptor (EGFR), which activates STAT3, is reportedly overexpressed in human pancreatic cancer cells [ xref ]."
30400136
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"Because lung cancer cell lines with elevated Stat3 expression demonstrated robust Stat3 feedback activation upon MEK inhibitor treatment, we examined a potential relationship between Stat3 expression [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25065853
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"A loss of functional STAT1 has been associated with the upregulation of EGFR, which may indirectly activate STAT3 constitutively."
34081439
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"How JSRV Env activates STAT3 is not known, but since the EGFR activated STAT3 pathway XREF_BIBR is important in NSCLC cell survival XREF_BIBR, Env induced activation of EGFR could be one mechanism."
23251519
sparser
"Both IL6ST and EGFR activate STAT3, allowing it to bind to the promoter region of the BAG4 gene, increasing expression[ xref ]."
27821646
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"EGFR stimulation has been shown to activate STAT3."
18997665
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"However, STAT1 and STAT3 have been shown to be activated by EGFR (epidermal growth factor receptor) and PDGFR (platelet-derived growth factor receptor), which are receptors with intrinsic tyrosine kinase activity, and by other non–receptor tyrosine kinases besides JAKs (13)."
36920781
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"These findings suggest the involvement of EGFR in alpha 1 -AR induced Stat3 activation."
18314882
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"In this study, we found that IGFBP2 facilitated the nuclear accumulation of EGFR, which promoted STAT3 transcriptional activity, resulting in increased IL-10, which is known to be a STAT3 downstream gene."
33309859
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"In addition, epidermal growth factor receptor (EGFR), which is known to activate STAT3, is critical for lung cancer metastasis XREF_BIBR."
30214629
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"Recently, it has been demonstrated that the intrinsic tyrosine kinase of the epidermal growth factor receptor directly activates STAT3 [51]."
9094433
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"In addition, the existence of EGFR independent signaling for Stat3 activation has been reported, enhancing the importance of Stat3 activation in tumor growth [XREF_BIBR]."
21197106
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"Collectively, in this work, we identified TPCA-1 as a direct dual inhibitor for both IKKs and STAT3, whereas treatment targeting EGFR only could not sufficiently repress NF-kappaB and STAT3 pathways for lung cancers harboring mutant EGFR."
24401319
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"In this study, we aimed to investigate the activity of Stat3 related activators such as EGFR and PI3K and Akt in the proliferation of a cutaneous malignant tumor, SCC, and evaluate the therapeutic value of inhibition of the signaling pathways."
21197106
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"Inhibitor of EGFR Downregulates the Constitutive Activation of Stat3 in HSC-1 Cells, and a Combination of Inhibitors of EGFR and PI3K and Akt Abrogates Stat3 Activation."
21197106
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"Surprisingly, it has been observed that EGFR TKIs (e.g., erlotinib) induce feedback activation of STAT3 signaling in EGFR-mutant cell lines via autocrine- and paracrine-secreted factors such as IL-6, leading to increased numbers of resistant cells [19, 22]."
34773474
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"EGFR signaling in myeloid cells promoted activation of STAT3 and expression of survivin in intestinal tumor cells."
28400195
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"For example, the Src and EGF receptor tyrosine kinases, both of which induce Stat3, are frequently activated in breast carcinoma and other tumor cells (Garcia et al. 1997; Sartor et al. 1997; Garcia a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
10023775
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"Growth-promoting signaling pathways including mitogen activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and Stat3, activated by EGFR, VEGFR2 and PDGFRs are key mediators of the normal healing process."
25266258
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"Although the mechanisms by which peptides promote wound-healing are not fully characterized, some studies have demonstrated that HDPs such as β-defensins promote keratinocyte migration through phospho[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25113635
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"A recent study by Quadros et al. [ xref ] has shown that EGFR-dependent Stat3 activation is observed only in SCC cell lines but not in HaCaT cells, because EGF did not activate Stat3 in HaCaT cells."
21197106
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"Furthermore, we found that FIP-nha decreased the phosphorylation of EGFR, STAT3 and Akt and inhibited activation effect of ligand factor EGF to EGFR and its downstream signal molecule STAT3 and Akt."
35415679
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"Because EGFR signaling was reported to activate Stat3, we examined the effect of EGF on Stat3 activation in these cells."
20959490
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"Of which, the EGFR and HER2 can activate STAT3 via phosphorylation through SRC to promote cell survival (Kavarthapu et al., 2021)."
36689784
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"An early hypothesis suggested that pStat3 is activated by deregulation of EGFR and aberrant IL-6 expression [XREF_BIBR]."
19421400
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"The above findings indicated that FIP-nha inhibited the growth of gastric cancer and induced apoptosis and autophagy through competitively binding to EGFR with EGF to blocking the EGFR-mediated STAT3/Akt pathway."
35415679
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"Myeloid cell expression of EGFR increases activation of STAT3 and expression of survivin in intestinal epithelial cells andexpression of IL6 in colon tissues."
28400195
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"This suggests the presence of an EGFR independent activation of Stat3 in HSC-1 cells."
21197106
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"XREF_BIBR - XREF_BIBR Notably, the activation of EGFR finally triggers PI3K/Akt/mTOR and STAT3 signaling pathways, resulting in increased cell survival by activating antiapoptotic proteins."
29593419
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"STAT3 is robustly activated by EGFR, and this activation is sustained due to strong positive feedback from STAT3 to EGFR ( xref A)."
39001416
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"Honokiol treatment suppressed lung cancer by inhibiting EGFR, which in turn reduced the extression of pSTAT3 [238] ."
28807562
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"XREF_BIBR, XREF_BIBR, XREF_BIBR In addition to IL-6, STAT3 can also be activated by EGFR that is often overexpressed in head and neck cancer cells."
29204553
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"Indeed, Li and colleagues (24) suggest that highly expressed IGFBP2 acts as a hub for multiple signaling pathways.In melanoma, IGFBP2 plays additional roles in the activation of the Epidermal Growth Factor Receptor (EGFR)-Signal Transducer adn Activator of Transcripton (STAT3) pathway, activating Programmed Death Ligand 1 (PDL1), and contributing to angiogenesis (24)."
39007351
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"Other investigators have reported similar findings, showing that STAT3 has been linked to EGFR, where EGFR can activate STAT3, thus contributing to cancer progression."
36977736
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"Similarly, an inhibitor of EGFR was shown to inhibit Stat3 activation and it was shown that high EGFR was positively correlated with Stat3 in breast cancer [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."
17531096
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"The proliferation and survival of myeloma cells may be suppressed by PD153035 due to the blockage of phosphatation of STAT3 induced by the activation of EGFR."
15562758
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"EGFR phosphorylates and activates STAT3, which, in turn, binds to and increases the transcriptional activation of the AR [ xref ]."
34064004
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"EGFR overexpression can activate NF-kappaB and STAT3, which leads to chemoresistance and poor outcome."
28938696
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"Although high levels of activated STAT3 occur in cells with activating mutation of EGFR, we did not believe that STAT3 activity is driven directly by EGFR kinase activity."
21216930
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"Additionally, STAT 1 inhibition is associated with epidermal growth factor receptor (EGFR) overexpression, which leads to STAT3 supplementary activation [28]."
38540252
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"It has been shown that the crosstalk between TAMs and tumor cells can regulate the induction of pluripotency gene SOX-2 through EGF receptor mediated activation of STAT3 signaling [XREF_BIBR]."
24088077
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"The findings reveal a novel mechanism where H3K23ac/TRIM24 mediates EGFR-induced STAT3 activation, enhancing the oncogenic potential of the EGFR/STAT3 pathway in human cancer [59]."
39160596
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"In vitro activation of Stat3 by epidermal growth factor receptor kinase."
8942998
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"EGFR Signaling in Myeloid Cells Promotes STAT3 Activation in Colorectal Tumor Cells."
28400195
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"The abundance of STAT3 in the particulate compartment (presumably representing nuclear localization) in early pregnancy (Fig. 7) makes perfect sense since STAT3 is activated by EGF-R which, as noted[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
11728516