◀ Back to EGFR
EGFR — STAT3
Pathways - manually collected, often from reviews:
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OpenBEL Selventa BEL large corpus:
STAT3
→
EGFR
(increases, EGFR Activity, STAT3 Activity)
Evidence: To explore this further, we have blocked endogenous ErbB3 transcription, thereby engineering tumor cells with overexpressed, fully active ErbB2 but lacking ErbB3 (T. Holbro and N.E. Hynes, unpublished data). As a consequence, these cells have decreased PI-3K/PKB signaling, a reduction in D-type cyclin levels, and show an increase in the G1 phase of the cell cycle. A main effector of ErbB signaling, the PI-3K/PKB pathway, is particularly important in mediating cell survival 103 T. Holbro et al. /...
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OpenBEL Selventa BEL large corpus:
STAT3
→
EGFR
(increases, EGFR Activity, STAT3 Activity)
Shi et al., J Biol Chem 2004*
Evidence: These results indicate that Pyk2 facilitates EGFR- and c-Src-mediated Stat3 activation, thereby implicating Pyk2 activation as a potential co-mediator in triggering Stat3-induced oncogenesis.
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OpenBEL Selventa BEL large corpus:
STAT3
→
EGFR
(increases, STAT3 Activity)
Evidence: This is taken from supplemental table 2 from PMID 15951569 Cut-offs were 2.25 for increase and 0.5 for decrease LLID were found by converting from GI assession numbers in DAVID Spreadsheet is saved in the project folder for Cell Signaling Project # bduckworth
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OpenBEL Selventa BEL large corpus:
STAT3
→
EGFR
(increases, STAT3 Activity)
Evidence: In this paper, we present a comprehensive pathway map of EGFR signaling and other related pathways.
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BioCarta egf signaling pathway:
EGF/EGF-R complex (EGF-EGFR)
→
STAT3
(modification, activates)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
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IRef Bind Interaction:
STAT3
—
EGFR
Shao et al., Cancer Res 2003*
-
IRef Bind_translation Interaction:
STAT3
—
EGFR
(experimental interaction detection)
Shao et al., Cancer Res 2003*
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IRef Bind_translation Interaction:
STAT3
—
EGFR
(affinity chromatography technology)
Shao et al., Cancer Res 2003*
-
IRef Bind_translation Interaction:
STAT3
—
EGFR
(coimmunoprecipitation)
Shao et al., Cancer Res 2003*
-
IRef Bind_translation Interaction:
STAT3
—
EGFR
(coimmunoprecipitation)
Lo et al., Cancer Cell 2005*
-
IRef Biogrid Interaction:
STAT3
—
EGFR
(colocalization, imaging technique)
Lo et al., Cancer Cell 2005*
-
IRef Biogrid Interaction:
STAT3
—
EGFR
(physical association, affinity chromatography technology)
Crovello et al., J Biol Chem 1998
-
IRef Biogrid Interaction:
STAT3
—
EGFR
(physical association, affinity chromatography technology)
Jaganathan et al., PloS one 2011*
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IRef Biogrid Interaction:
STAT3
—
EGFR
(physical association, affinity chromatography technology)
Andl et al., Am J Physiol Gastrointest Liver Physiol 2004
-
IRef Biogrid Interaction:
STAT3
—
EGFR
(colocalization, imaging technique)
Lo et al., Mol Cancer Res 2010*
-
IRef Biogrid Interaction:
STAT3
—
EGFR
(physical association, affinity chromatography technology)
Foerster et al., Proteomics 2013
-
IRef Biogrid Interaction:
STAT3
—
EGFR
(physical association, affinity chromatography technology)
Yuan et al., Mol Cell Biol 2004*
-
IRef Biogrid Interaction:
STAT3
—
EGFR
(physical association, affinity chromatography technology)
Olayioye et al., J Biol Chem 1999
-
IRef Biogrid Interaction:
STAT3
—
EGFR
(physical association, affinity chromatography technology)
Lo et al., Cancer Cell 2005*
-
IRef Hprd Interaction:
STAT3
—
EGFR
(in vitro)
Shao et al., Cancer Res 2003*
-
IRef Intact Interaction:
Complex of 12 proteins
(association, tandem affinity purification)
Li et al., Molecular systems biology 2013
-
IRef Intact Interaction:
Complex of UBASH3B-CDC37-EGFR-ERBB3-ERRFI1-SHC1-ERBB2-STAT3
(association, anti bait coimmunoprecipitation)
Li et al., Molecular systems biology 2013
-
IRef Intact Interaction:
STAT3
—
EGFR
(association, pull down)
Shao et al., J Biol Chem 2004*
-
IRef Intact Interaction:
Complex of 70 proteins
(association, anti bait coimmunoprecipitation)
Thelemann et al., Mol Cell Proteomics 2005
-
IRef Ophid Interaction:
STAT3
—
EGFR
(aggregation, confirmational text mining)
Jones et al., Nature 2006
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IRef Ophid Interaction:
STAT3
—
EGFR
(aggregation, interologs mapping)
Brown et al., Bioinformatics 2005
Text-mined interactions from Literome
Song et al., Oncogene 2000
(Head and Neck Neoplasms) :
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
Garcia et al., Oncogene 2001
(Breast Neoplasms) :
While
EGF-R kinase activity is not
required for constitutive
Stat3 activation in breast cancer cells, EGF stimulation further increases STAT DNA binding activity, consistent with an important role for EGF-R in STAT signaling and malignant progression
Berclaz et al., Int J Oncol 2001
(Adenocarcinoma, Mucinous...) :
EGFR dependent expression of
STAT3 ( but not STAT1 ) in breast cancer
Sriuranpong et al., Cancer Res 2003
(Carcinoma, Squamous Cell...) :
Even in the EGFR positive cell lines,
STAT3 activation was not
dependent on
EGFR activation, as STAT3 tyrosine phosphorylation levels persisted after treatment with AG1478, a chemical inhibitor of EGFR activity
Shao et al., Cancer Res 2003
(Carcinoma, Squamous Cell) :
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 ... 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 ... When delivered into squamous carcinoma cells, phosphopeptides spanning Y1068 and Y1086 were able to inhibit
EGFR stimulated
Stat3 DNA binding activity and cell proliferation
Zhang et al., Biochem J 2003
:
Indeed, Grb2
inhibits the interaction between
Stat3 and EGFR by competitive binding to the
EGFR
Shi et al., J Biol Chem 2004
:
Here, we provide evidence that Pyk2, along with c-Src, facilitates
EGFR mediated
Stat3 activation
Chan et al., Cancer Res 2004
(Skin Neoplasms) :
Epidermal growth factor receptor mediated activation of
Stat3 during multistage skin carcinogenesis ... Several approaches were used to examine the possible
role of
epidermal growth factor receptor (EGFR) in modulating
Stat3 activity during tumor promotion
Quadros et al., Cancer Res 2004
(Carcinoma, Squamous Cell...) :
Here, we show that
EGFR dependent
STAT3 activation is restricted to malignant keratinocytes ...
EGFR dependent activation of mitogen activated protein kinase ( MAPK ) kinase 1 negatively
regulated STAT3-Y705 phosphorylation in normal and malignant keratinocytes ... Together, these results underscore that
EGFR activation is
required but not sufficient for
STAT3 activation to occur in malignant keratinocytes
He et al., Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2004
(Multiple Myeloma) :
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
Hambek et al., Anticancer Res 2004
(Carcinoma, Squamous Cell...) :
STAT 3 activation in head and neck squamous cell carcinomas is
controlled by the
EGFR
Ghosh et al., Oncogene 2005
(Glioblastoma) :
PI3K-AKT pathway negatively controls
EGFR dependent DNA binding activity of
Stat3 in glioblastoma multiforme cells
Lee et al., Mol Cancer Ther 2006
(Carcinoma, Squamous Cell...) :
Epigenetic modification of SOCS-1 differentially regulates
STAT3 activation in
response to interleukin-6 receptor and
epidermal growth factor receptor signaling through JAK and/or MEK in head and neck squamous cell carcinomas ... 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 ... We investigated whether epigenetic modification of SOCS-1 affects
STAT3 activation in
response to IL-6R-,
EGFR- , JAK-, or mitogen activated protein kinase/extracellular signal regulated kinase kinase ( MEK ) -mediated signal activation ... In UMSCC-11A cells with unmethylated SOCS-1,
STAT3 activation was
regulated by both
EGFR and IL-6R via a JAK independent pathway involving MEK ... 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
Alvarez et al., Cancer Res 2006
(Carcinoma, Non-Small-Cell Lung...) :
In non-small-cell lung cancer cells,
STAT3 activity is
regulated by
EGFR through modulation of STAT3 serine phosphorylation
Suzuki et al., Mod Pathol 2006
(Carcinoma, Non-Small-Cell Lung...) :
In five cases of carcinomas with EGFR amplification,
EGFR expression and phosphorylation levels were higher than other cases, and
Stat-3 was
activated in all five cases
Cao et al., Am J Physiol Lung Cell Mol Physiol 2007
:
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
Onishi et al., Exp Cell Res 2008
(Carcinoma, Squamous Cell...) :
This intercellular adhesion induced
STAT3 activation was
mediated by JAK and Src signaling and partially by
EGFR signaling
Kung et al., J Virol 2008
:
Epstein-Barr virus latent membrane protein 1
induces expression of the
epidermal growth factor receptor through effects on Bcl-3 and
STAT3 ... A
STAT3 inhibitor significantly
reduced the activation of STAT3, as well as the CTAR1 mediated upregulation of Bcl-3 and
EGFR
Kim et al., Cell Signal 2009
(Breast Neoplasms) :
EGF also induced the phosphorylation of EGFR, ERK, and
STAT-3 , and these effects were
inhibited by the
EGFR inhibitor, AG1478.To investigate the involvement of the STAT-3 pathway on EGF induced MMP-9 expression, we pretreatedSKBR3 cells with JAK1, JAK2, and JAK3 inhibitors prior to EGF treatment
Lee et al., The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 2008
:
In the present study, we found that specific tyrphostin inhibitors of ErbB2 ( AG825 and AG879 ), but not
ErbB1 inhibitor ( AG1478 ),
suppressed IL-6 induced tyrosine phosphorylation of
STAT3 in schwannoma cells
Jaganathan et al., J Pharmacol Exp Ther 2010
(Pancreatic Neoplasms) :
Constitutively active Stat3 is sensitive to both EGFR and Src inhibition, but the early suppression of aberrantly active
Stat3 in
response to the inhibition of
EGFR and Src is countered by a Janus kinase ( Jaks ) -dependent reactivation, suggesting that Jaks activity is a compensatory mechanism for Stat3 induction
Lin et al., Dev Biol 2010
(Skin Diseases) :
Both Tyrphostin AG1478, an
EGFR tyrosine kinase inhibitor, and curcumin, an
inhibitor of both
STAT3 and EGFR, attenuated STAT3 activation/nuclear translocation, reduced skin thickening, and partially suppressed the barrier abnormalities
Haura et al., J Thorac Oncol 2010
(Adenocarcinoma...) :
Persistent
STAT3 may be
leading to primary resistance to
EGFR inhibitors in vivo
Bito et al., Journal of skin cancer 2011
:
These data suggest that
Stat3 activation through
EGFR and/or PI3K/Akt activation plays a critical role in the proliferation and survival of human cutaneous SCC
Nagaraj et al., Clin Cancer Res 2011
(Pancreatic Neoplasms) :
Furthermore, combined inhibition of Src and
EGFR with gemcitabine
inhibited constitutively activated
STAT3 in vitro and in vivo
Kung et al., J Virol 2011
:
EGFR transcription is induced by LMP1 through a p50 NF?B1-Bcl-3 complex, and Bcl-3 is
induced by LMP1 mediated activation of
STAT3
Li et al., Am J Physiol Heart Circ Physiol 2011
(Cardiomegaly...) :
Transactivated
EGFR mediates a1-AR induced
STAT3 activation and cardiac hypertrophy ... Furthermore, the a ( 1 ) -AR activated STAT3 was associated with transactivation of EGFR because inhibition of
EGFR with the selective inhibitor AG1478
prevented a ( 1 ) -AR induced
STAT3 tyrosine phosphorylation and its transcriptional activity, as well as cardiac hypertrophy
Luwor et al., Oncogene 2013
(Neoplasms) :
We identified
Stat3 , which is
activated specifically and persistently by overexpressed
EGFR , as a key signaling molecule responsible for the reduced TGF-ß sensitivity
Kotipatruni et al., PloS one 2012
(Disease Progression...) :
The apoptosis induced by targeting MMP-9 and uPAR was initiated by inhibiting
epidermal growth factor receptor (EGFR) mediated activation of
STAT3 and NF-?B related signaling molecules
Ripamonti et al., J Cell Physiol 2013
(Carcinoma, Squamous Cell) :
RNA interference experiments suggested the
role of
STAT3 in regulating dNp63a expression downstream of
EGFR ... Together, our findings provide evidence that dNp63a expression is regulated by
EGFR activation through
STAT3 and that the EGFR-dNp63a axis is crucial for proliferation of TICs present in SCCs. J. Cell
Park et al., Proc Natl Acad Sci U S A 1996
:
In vitro
activation of
Stat3 by
epidermal growth factor receptor kinase