IndraLab

Statements

EGFR phosphorylates STAT3. 98 / 99
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"In cervical squamous cell carcinoma, CD109 expression enhanced EGFR-induced phosphorylation of STAT3, resulting in increased tumor aggressiveness and stemness activity [ xref ]."
33375719
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"Since EGFR and ERK can directly phosphorylate and activate STAT3, we hypothesized that RPN2 might modulate the activity of STAT3 by EGFR glycosylation."
32404045
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"However, we found that TRIM59 overexpression significantly suppressed the interaction of TC45 and STAT3, but increased STAT3 phosphorylation stimulated by EGFRvIII ( xref )."
29386185
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"Epidermal growth factor receptor (EGFR)-independent phosphorylation of STAT3 (P-STAT3) has been identified as a mechanism of tumor resistance to agents targeting SFK."
21266530
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"In addition, inhibition of EGFR blocked BI-induced Src, Jak2, and STAT3 phosphorylation."
21536676
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"EGFR mediated tumor immunoescape : The imbalance between phosphorylated STAT1 and phosphorylated STAT3."
24501692
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"These results indicate that EGFRvIII enhances STAT3 transcription and phosphorylation in HNSCC, effects that are resistant to treatment with cetuximab."
20622897
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"Meanwhile, Stat3 phosphorylation can be promoted by EGFR ( xref )."
35252007
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"In addition, STAT3 functions downstream of the EGFR, and EGFR blocking further inhibits STAT3 phosphorylation."
34220520
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"On the cell surface, activated EGFR recruits and phosphorylates STAT3 at Y705, and in turn, phosphorylated STAT3 (p-STAT3) enters the nucleus to activate expression of several cancer-related genes ( xref )."
18829483
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"Newly synthesized IL-6 drives association of the IL-6 receptor and gp130 with EGFR, leading to EGFR dependent rephosphorylation of STAT3, which is not inhibited by the continued presence of SOCS3."
24082147
sparser
"As both EGFR and IL-6R promote STAT3 phosphorylation, simultaneously targeting both pathways by inhibiting a common downstream molecule stands out as the most logical strategy to reverse immunosuppressive activity of STAT3."
24501692
sparser
"EGFR phosphorylates and activates STAT3, which, in turn, binds to and increases the transcriptional activation of the AR [ xref ]."
34064004
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"Epidermal growth factor receptor and certain other receptor tyrosine kinases, such as c-MET, phosphorylate STAT3 in response to their ligands XREF_BIBR."
22114683
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"The C-E-Cad 14-aa tail enables direct binding to the CR2 domain of full-length EGFR through salt bridge and hydrogen bond interactions, accompanied by EGFRvIII to promote STAT3 phosphorylation and nuclear translocation and AKT and ERK1/2 phosphorylation, resulting in the tumorigenicity of GBM [46, 105]."
| PMC
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"The C-E-Cad 14-aa tail enables direct binding to the CR2 domain of full-length EGFR through salt bridge and hydrogen bond interactions, accompanied by EGFRvIII to promote STAT3 phosphorylation and nuclear translocation and AKT and ERK1/2 phosphorylation, resulting in the tumorigenicity of GBM [46, 105]."
| PMC
rlimsp
"In this issue of Cancer Cell, Weiss and colleagues implicate phosphorylation of EGFRvIII by EGFR and the consequent phosphorylation of STAT3 as a signaling axis that drives transformation in glioblastoma."
24135276
rlimsp
"When expression of ezrin was inhibited, EGFR activity and phosphorylation levels of downstream signaling pathway proteins ERK and STAT3 were decreased."
26936397
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"Cetuximab, by blocking the ligand-to-receptor access, prevents compensatory EGFR activation and phosphorylation of STAT3 [XREF_BIBR] in response to radiation induced damage."
19236156
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"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
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"EGFR activation also leads to phosphorylation of STAT3."
24048704
sparser
"ErbB1 is able to phosphorylate STAT1 and STAT3 in vitro [ xref , xref ]."
25126546
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"EGFR overexpression increased the phosphorylation of EGFR, Akt, and STAT3 signaling proteins and could partly restored the inhitory effect of MSA treatment, including the phosphorylation of EGFR, Akt, STAT3 (XREF_FIG) and IL-6 mRNA levels in both KYSE150 and KYSE 510 cells (XREF_FIG)."
34393797
sparser
"Stat3 can be phosphorylated by activated EGFR and promote tumor survival in vivo in NSCLC [ xref ]."
23937717
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"This was a result of impaired shedding of EGF-R ligands resulting in failure to phosphorylate STAT3 via the EGF-R and, consequently, in defective regeneration of epithelial cells and breakdown of the intestinal barrier."
20603312
rlimsp
"Genistein inhibited the phosphorylated Stat3 but did not affect EGFR autophosphorylation."
17074332
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"STAT3 Phosphorylation is Triggered by JAK but Not Src or EGFR in NHE1 Overexpressed Gastric Cells."
32904684
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"XREF_BIBR EGFR can directly phosphorylate STAT3, and activation of STAT3 has also been reported in NSCLC cell lines harboring activated EGFR mutations."
| PMC
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"As both EGFR and IL-6R promote STAT3 phosphorylation, simultaneously targeting both pathways by inhibiting a common downstream molecule stands out as the most logical strategy to reverse immunosuppressive activity of STAT3."
24501692
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"Consistent with this observation, PEDV infection rapidly induced STAT3 phosphorylation in IPEC-DQ cells (Fig. 5A) but did not increase but rather slightly decreased JAK1 and JAK2 phosphorylation, suggesting that STAT3 phosphorylation is mediated by EGFR."
| PMC
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"Cell-surface EGFRvIII also interacts with and phosphorylates STAT3."
20030624
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"Western blots confirmed decreased pJAK2, total JAK2 (tJAK2) and pSTAT3 in NPcis; Wa2/+ mouse GEM-PNST tumors compared to the NPcis GEM-PNSTs (XREF_FIG), suggesting that the decrease of pSTAT3 (Tyr 705) is attributed at least in part JAK2, but we can not exclude the possibility that the STAT3 is directly phosphorylated and activated by EGFR."
23318430
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"In addition, the presence of EGFR in CHO cells markedly enhanced T. gondii induced early Y705 STAT3 phosphorylation (XREF_SUPPLEMENTARY)."
29036202
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"Since we found that irradiation specifically suppressed STAT1 and STAT3 phosphorylation in IFNγ-treated A549 cells in this study, we speculated that STAT3 caused radioresistance was mediated by overexpression and activation of mutated EGFR in lung cancer after survived in RT treatment.Since the characteristic of autophosphrylation of EGFR exon 19 deletion, EGF did not affect STAT3 phosphorylation but IFNγ caused highly STAT3 phosphorylation in HCC827."
| PMC
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"In other studies, cells were treated with various specific pharmacological inhibitors where phosphorylation of Stat3 was not reduced by epidermal growth factor receptor and Mitogen activated protein and extracellular signal regulate kinase kinase (MEK1/2) inhibitors, suggesting lack of significant roles of these in Stat3 activation in DU145 cells."
17341659
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"ERBB inhibition blocked phosphorylation of STAT3 and arrested cancer cells."
30645971
rlimsp
"Stat3 can be phosphorylated by activated EGFR and promote tumor survival in vivo in NSCLC [35]."
23937717
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"The PE induced Stat3 phosphorylation was blocked by the EGFR kinase inhibitor, AG1478, in both primary hepatocytes and Hep3B cells (XREF_FIG)."
18314882
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"EGFR independent phosphorylation of STAT3 (P-STAT3) has been identified as a mechanism of tumor resistance to agents targeting SFK."
21266530
signor
"The transcription factors stat1, stat3, and stat5 are directly phosphorylated by erbb-1, subsequent to which they dimerize through phosphotyrosine-sh2 domain interactions and translocate to the nucleus to activate gene trascription critical for proliferation."
14967450
sparser
"Epidermal growth factor receptor (EGFR)-independent phosphorylation of STAT3 (P-STAT3) has been identified as a mechanism of tumor resistance to agents targeting SFK."
21266530
sparser
"Moreover, STAT3 tyrosine phosphorylation can also be stimulated by EGFR through recruiting to the membrane receptors, except for cytokines, Janus-activated kinases (JAK) and Src family kinases xref , xref , xref , xref ."
33391507
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"Interestingly, there is some dichotomy between RAS and EGFR mutations in lung tumors [ xref ] and EGFR can promote STAT3 phosphorylation and signaling [ xref , xref ]."
24833526
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"Significantly, ZD6474 effectively suppressed EGFRvIII stimulated protein phosphorylation of Stat3 and Akt and protein expression of Bcl-X L in U87MG and EGFRvIII glioma cells that retained EGFRvIII expression in vitro and in vivo (XREF_FIG), whereas minimal effect was found in parental U87MG glioma cells lacking EGFRvIII (XREF_FIG)."
20371720
reach
"Interestingly, EGFR independent phosphorylation of STAT3 has been identified as a mechanism of tumor resistance to agents targeting SFK [XREF_BIBR]."
25779657
rlimsp
"Treatment of cells with TKS050 resulted in a dose-dependent inhibition of EGFR autophosphorylation and of phosphorylated signal transducer and activator of transcription 3 (Stat3)."
17074332
rlimsp
"Immunoblotting analysis indicated that AG1478 effectively inhibited epidermal growth factor receptor autophosphorylation, that AG490 decreased the level of Jak2 and phosphorylated Stat3, and that PP2 decreased the level of pp60Src protein."
12748499
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"STAT3 can also be directly phosphorylated and activated by EGFR."
29321659
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"Mechanistically, ZD6474 inhibits autotyrosine phosphorylation of EGFR and EGFRvIII, suppresses EGFR dependent and EGFRvIII dependent phosphorylation of Stat3, Akt, and ERK1 / 2, and reduces expression of Bcl-X L in EGFRvIII expressing glioma cells."
20371720
reach
"EGFR signaling could induce the phosphorylation of pro survival STAT3, ERK1/2 and Akt, which contributes significantly to GBM cell proliferation [XREF_BIBR]."
26830677
sparser
"It also inhibits phosphorylation of EGFR ( xref ) and JAK2 ( xref ) and inhibits the tyrosine kinase activities of the EGFR ( xref ) and Src ( xref ), both of which can phosphorylate STAT3."
20513444
sparser
"Recently, EGFR-induced STAT3 phosphorylation in breast cancer was found to be dependent on suppressing TC45 dephosphorylation of nuclear STAT3 ( xref )."
29386185
sparser
"Then, we performed Western blotting assays and found that compared with the controls, depletion of TRIM59 in EGFRvIII-expressing cells markedly inhibited EGFRvIII-promoted STAT3 phosphorylation ( xref )."
29386185
sparser
"Curcumin ( xref ) is known to inhibit STAT3 phosphorylation by EGFR, Src, and Jak2, the upstream kinases responsible for activation of STAT3 whereas AG490 ( xref ) is a specific inhibitor of Jak2 kinase which is primarily responsible for STAT3 phosphorylation through IL-6 receptor."
23874455
signor
"The transcription factors stat1, stat3, and stat5 are directly phosphorylated by erbb-1, subsequent to which they dimerize through phosphotyrosine-sh2 domain interactions and translocate to the nucleus to activate gene trascription critical for proliferation."
22693070
isi
"Mechanistically, we found that GOLM1 promotes the phosphorylation of STAT3 by enhancing the level of EGFR, which in turn upregulates the transcriptional expression of PD-L1."
33294262
sparser
"STAT3 can be tyrosine-phosphorylated by the dimerized epidermal growth factor receptor (EGFR), EGFR-activated SRC (8, Fig. 3), or by EGFR-activated JAK2 [62], but only the latter pathway is regulated by SOCS3."
33037393
sparser
"Furthermore, previous studies reported that STAT3 interact with EGFR through its SH2 domain, and the bound EGFR reciprocally phosphorylates STAT3 and induces its dimerization."
28783167
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"As a tyrosine kinase receptor, EGFR is capable to induce STAT3 phosphorylation."
34393797
sparser
"EGFR inhibitor promoted phosphorylation of Stat3 in pancreatic cancer cells."
31572001
sparser
"Epidermal growth factor receptor and certain other receptor tyrosine kinases, such as c-MET, phosphorylate STAT3 in response to their ligands xref ."
22114683
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
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"PD153035, a specific inhibitor of EGFR, effectively blocked the phosphorylation of EGFR and STAT3, and proliferation of C6st-1 KO keratinocytes was lowered to the same level as that of C6st-1 WT keratinocytes."
33495490
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"This process is not a result of increased EGFR expression, but rather an optimization of EGFR organization at the plasma membrane, thus enhancing EGFR phosphorylation and subsequent STAT3 signal transduction and VEGF-A secretion."
25272226
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"Activation by IL6 is mediated by members of the JAK kinase family; the tyrosine kinases EGFR and SRC can directly phosphorylate STAT3."
22348200
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"The mechanism may be that inhibition of core fucosylation of the EGF receptor inactivates the EGF signaling pathway by suppressing the phosphorylation of STAT3 and NF-κB in the peritoneal membrane of rats with peritoneal fibrosis, although further investigation is required.Figure 1."
33993842
reach
"In the current study, specific inhibitors of EGFR and Src decreased IR-induced phosphorylation of STAT3, resulting in reduced invasion and suppression of EMT (Figure 2)."
32605153
reach
"EGFR signaling inhibition caused a decrease of phosphorylation of p-Stat3 in case 2 and c-CSC3, conversely in p-CSC1 and p-CSC3 the levels of p-Stat3 were unmodulated, suggesting a mechanism of resistance to EGFR TKI treatment in these cases."
25380967
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"In EGFR as3 / EGFRvIII cells, 4TB blocked phosphorylation of EGFR as3, EGFRvIII, and STAT3, consistent with EGFRvIII phosphorylation by EGFR (XREF_FIG)."
24135280
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"Furthermore, previous studies reported that STAT3 interact with EGFR through its SH2 domain, and the bound EGFR reciprocally phosphorylates STAT3 and induces its dimerization."
28783167
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"ErbB1 is able to phosphorylate STAT1 and STAT3 in vitro [XREF_BIBR, XREF_BIBR]."
25126546
sparser
"Activation by IL-6 is mediated by members of the JAK kinase family; the tyrosine kinases EGFR and Src can directly phosphorylate STAT3 [ xref ]."
23333246
biopax:netpath
No evidence text available
12070153
reach
"Our results support a model where inhibition of EGFR signaling impairs STAT3 phosphorylation, leading to enhanced IRG expression and antiviral activity."
23519785
sparser
"Activation by IL6 is mediated by members of the JAK kinase family; the tyrosine kinases EGFR and SRC can directly phosphorylate STAT3."
22348200
reach
"The mechanism may be that inhibition of core fucosylation of the EGF receptor inactivates the EGF signaling pathway by suppressing the phosphorylation of STAT3 and NF-jB in the peritoneal membrane of rats with peritoneal fibrosis, although further investigation is required.Fut8 expression was upregulated in the peritoneum of peritoneal fibrosis (PF) rats."
33993842
reach
"Further mechanistic studies suggested that the activation of EGFR activated its downstream JAK/STAT3 signaling pathway and promoted STAT3 phosphorylation; the phosphorylated STAT3 transcriptionally promoted the levels of UTX."
34661759
sparser
"EGFR can directly phosphorylate STAT3 and activation of STAT3 has also been reported in lung cancer cell lines harboring activated EGFR mutations ( xref , xref , xref , xref , xref )."
21216930
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"Stat3 can be phosphorylated by activated EGFR and promote tumor survival in vivo in NSCLC [XREF_BIBR]."
23937717
sparser
"Most importantly, fucoxanthin inhibited the expressions of the epidermal growth factor receptor (EGFR) and STAT3 and phosphorylated STAT3 proteins."
23118721
reach
"Activation by IL-6 is mediated by members of the JAK kinase family; the tyrosine kinases EGFR and Src can directly phosphorylate STAT3 [XREF_BIBR]."
23333246
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"EGFR and KRAS mutations do not enrich for the activation of IL-6, JAK1 or phosphorylated STAT3 in resected lung adenocarcinoma."
28879441
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"It also inhibits phosphorylation of EGFR and JAK2 and inhibits the tyrosine kinase activities of the EGFR and Src, both of which can phosphorylate STAT3."
20513444
reach
"In one study, using lung carcinoma cell line, EGFR inhibition did not block STAT3 phosphorylation and growth arrest, suggesting that upstream pathways, such as JAK and IL6 receptor, may play a role in activating STAT3 and contributing to oncogenesis in lung tumors, even with EGFR activation [XREF_BIBR]."
25763322
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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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"Receptor tyrosine kinases, EGFR and c-Met, phosphorylate Stat3 upon ligand binding."
22077153
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"EGFR can also directly phosphorylate Stat3 in vitro 55."
10974037
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"A novel approach using peptide aptamers that inhibit EGFR mediated phosphorylation of STAT3 have also been identified in a modified yeast two-hybrid screen [287]."
24388873
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"Cell-surface EGFRvIII also interacts with and phosphorylates STAT3."
20145033
sparser
"We established α5-nAChR-overexpressing or knockdown clones in LAC cell lines ( xref A) and found that α5-nAChR overexpression in LAC cell lines leads to enhanced EGFR phosphorylation as well as the phosphorylation of Akt and STAT3 ( xref B,C; xref A)."
32957649
sparser
"However, re-expression of shRNA-resistant TRIM59 Y218F/Q221A mutant did not restore EGFRvIII-induced STAT3 phosphorylation or target gene expression ( xref and xref ), suggesting that the Y218/Q221 sites are critical for TRIM59 interaction with STAT3."
29386185
reach
"Interestingly, there is some dichotomy between RAS and EGFR mutations in lung tumors [XREF_BIBR] and EGFR can promote STAT3 phosphorylation and signaling [XREF_BIBR, XREF_BIBR]."
24833526
reach
"EGFR forms a complex with and directly phosphorylates the transcription factor STAT3 [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
23590833
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"We conclude that Stat3 isoforms can be directly phosphorylated and thereby activated in vitro by the epidermal growth factor receptor kinase."
8942998
reach
"In lung adenocarcinoma, CINDy specifically highlights modulatory interactions that affect epithelial proliferation, such as the direct phosphorylation by the Epidermal Growth Factor Receptor (EGFR) of the STAT1 XREF_BIBR and STAT3 XREF_BIBR TFs, a fundamental and well established step in the proliferative signal transduction cascade that was not detected by MINDy."
25314274
reach
"In contrast, pStat3 level, which was higher in Gprc5a -/- cells than in Gprc5a +/+ cells before EGF treatment, decreased 30 min after EGF addition and began to increase slightly after 3 hours (XREF_FIG, middle) suggesting that EGFR activation does not mediate Stat3 phosphorylation in either of these cells."
20959490
reach
"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
sparser
"STAT3 can be tyrosine-phosphorylated by the dimerized epidermal growth factor receptor (EGFR), EGFR-activated SRC (8, Fig.  xref ), or by EGFR-activated JAK2 [ xref ], but only the latter pathway is regulated by SOCS3."
33037393