IndraLab
Statements
reach
"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."
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]."
reach
"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."
reach
"Additional transduction factors involved in LRG1 signalling include (i) EGFR which promotes pancreatic cancer cell malignancy through p38/MAPK [49], dissemination of melanoma cells [90] and cornea repair through STAT3 [64]; (ii) the IL-6/STAT3 axis which modulates neutrophil chemotaxis [57]; (iii) Wnt/βcatenin which, in the heart, inhibit fibroblast proliferation and migration [37]."
reach
"c-Src tyrosine kinase can constitutively activate STAT3, which increases the possibility of the STAT signaling pathway regulating tumor-related gene expression.155 Epidermal growth factor receptor can directly activate STAT1, STAT3, and STAT5, furthermore, STAT5 can be directly activated by the platelet-derived growth factor receptor.99,156,157In addition to the main components of the JAK/STAT signaling pathway, many related proteins play indispensable roles in STAT-dependent transcription and JAK–STAT interactions with other signaling pathways."
reach
"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)."
reach
"These include lonafarnib (RAS inhibitor), omipalisib (PI3K inhibitor), pictilisib (PI3K inhibitor), RO5126766 (RAF and MEK inhibitor), sorafenib (RAF inhibitor, STAT3 inhibitor [62]), because Ras/Raf/MAPK pathway [173] and PI3K pathway [174] are also involved in EGFR mediated STAT3 activation, these inhibitors can possibly synergistically potentiate IFN-I 's anti-SARS-CoV-2 activity.As noted above, PAI-1 is intimately involved in the pathogenesis of COVID-19, and its inhibition may be a key point at which to treat the disease once the escalating cycle between PAI-1 and STAT3 has been established."
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 )."
sparser
"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)."
reach
"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."
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."
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)."
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]."
reach
"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."
sparser
"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."
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."
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 )."
reach
"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
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."
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."
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."
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 ]."
reach
"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."
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 ]."
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."
reach
"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."
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."
reach
"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."
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."
sparser
"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 "
sparser
"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."
reach
"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."
sparser
"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)."
reach
"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)."
reach
"Pictilisib (IC 50 2.58 μM), a PI3K inhibitor, and omipalisib (IC 50 0.014 μM), a dual PI3K/mTOR inhibitor, inhibited viral replication in cells 115 EGFR-mediated STAT3 activation is controlled by the RAS/ RAF/MAPK and PI3K pathways, and inhibition of these pathways will potentiate IFN-1 and anti-SARS-CoV-2 activity in a synergistic manner."
reach
"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."
reach
"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."
reach
"These include lonafarnib (RAS inhibitor), omipalisib (PI3K inhibitor), pictilisib (PI3K inhibitor), RO5126766 (RAF and MEK inhibitor), sorafenib (RAF inhibitor, STAT3 inhibitor [62]), because Ras and Raf / MAPK pathway [173] and PI3K pathway [174] are also involved in EGFR mediated STAT3 activation, these inhibitors can possibly synergistically potentiate IFN-I 's anti-SARS-CoV-2 activity.As noted above, PAI-1 is intimately involved in the pathogenesis of COVID-19, and its inhibition may be a key point at which to treat the disease once the escalating cycle between PAI-1 and STAT3 has been established."
reach
"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."
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."
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]."
reach
"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]."