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ESR1 activates EGFR. 49 / 51
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"G-protein-coupled estrogen receptor (GPER and GPR30) was reported to bind 17beta-estradiol (E 2), tamoxifen, and ICI 182,780 (fulvestrant) and promotes activation of epidermal growth factor receptor (EGFR)-mediated signaling in breast, endometrial and thyroid cancer cells."
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"Interestingly, the selective estrogen receptor modulator (SERM) tamoxifen and the antiestrogen ICI 182,780 both promote GPR30 dependent transactivation of the EGF receptor and subsequent MAPK activation."
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"These results establish the interdependence of ERalpha and EGFR signaling, which may be mediated by cytosolic and ligand independent ERalpha."
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"Stimulation of ER has been reported to increase the activity of the EGFR signal, and EGFR signal increases the activity of the ER [XREF_BIBR]."
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"Moreover, the fact that activation of DeltaRaf : ER strongly induced the expression of growth factors of the EGF growth factor family suggests the existence of an autocrine loop through the activation of the EGF receptor : Activation of DeltaRaf : ER triggers the stimulatation of the EGF receptor."
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"The conjugated Er could mediate specific delivery of Cy7 to EGFR mutated NSCLC cells to enable targeted NIR fluorescence imaging and photothermal therapy (PTT)."
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"Membrane ER and GPER activate epidermal growth factor receptor (EGFR) with downstream signaling through Ras/Raf and mitogen-activated protein kinase (MAPK) ( xref )."
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"Activated membrane ER can then activate adjacent EGFR and/or HER2, which may then stimulate tumor growth."
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"Treatment with beta-estradiol increased secretion of VEGFA in NSCLC cells, which was largely mediated by ER activation of the EGFR."
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"Tamoxifen resistance is a complex progress involving the inappropriate activation of ER mediated epidermal growth factor receptor (EGFR) signaling pathway which promotes the proliferation and survival of cancer cells, rendering them cancer stem cell like properties [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"Differences in the average Ki67 reduction were particularly marked for ER positive tumors that overexpressed HER1 and/or HER2 (88 versus 45%, respectively; P = 0.0018)."
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"Alternatively, a cell membrane associated form of ER (mER) has been reported to couple with and activate various G proteins, and thereby mediate the EGFR transactivation, serving as a nongenotropic effect of the ER."
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"It is well-documented that ERα indirectly activates EGFR through MMP-9- and MMP-2-catalyzed release of HB-EGF ( xref ; xref )."
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"Poised as an alternative estrogen receptor that is activated by ER antagonists to promote EGFR transactivation, GPER, in part, may provide a rational explanation for this observation."
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"Although different growth factors may induce EGFR dimers possessing different equilibrium or kinetic stability, with ER and EPI inducing EGFR dimers with low stability, and EGF and other growth factor[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Interestingly, the selective estrogen receptor modulator (SERM) tamoxifen and ER antagonist ICI 182,780 both promote GPR30 dependent transactivation of the EGF receptor and subsequent MAPK activation."
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"Though nominally classified as a diagnosis of exclusion (thus " triple negative "), TNBC tumors frequently (72-75%) [XREF_BIBR] overexpress epidermal growth factor receptor (EGFR), whereas only a minority (16%) of ER positive breast cancers overexpress EGFR [XREF_BIBR, XREF_BIBR]."
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"Interactions of ERα with the kinase c-Src were found to enable the activation of EGFR by ERα."
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"Nongenomic signaling involving EGFR activation by ERs is a predominant signaling pathway in NSCLC and may portend a poor prognosis [ xref , xref ]."
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"Furthermore, this response requires SRC and phosphorylated SHC-adaptor protein (Shc), and is dependent upon transactivation of EGFR via release of HB-EGF [XREF_BIBR], similar to the mechanism observed for ERalpha induced EGFR transactivation in MCF7 breast cancer cells by Razandi et al. [XREF_BIBR]."
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"Recently it has been demonstrated that estrogen can induce gene expression and increase migration in mammary CAFs by an ERalpha independent pathway through GPR30 mediated transactivation of EGFR leading to activation of ERK XREF_BIBR."
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"The stimulation of ER increases the activity of EGFR signal and the signal of EGFR increases the activity of ER [7]."
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"ER down regulation by siRNA also induced EGFR activation and ligand expression in MCF-7L cells."
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"ER down regulation by siRNA induced similar EGFR activation and regulation of EGFR ligands as fulvestrant."
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"3,4 Approximately 10% of ER + tumors overexpress human epidermal growth factor receptor 2 (HER2), and tumors co-expressing ER and HER2 exhibit a more aggressive phenotype and are less responsive to ta[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"ERα can also directly activate the epidermal growth factor receptor (EGFR), causing activation of the MAPK and PI3K pathways xref , xref ."
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"By means of siRNA mediated downregulation of CD44 expression and blocking experiments, we identified CD44v6 as a co-receptor for EGF- and ER induced ErbB1 activation and for NRG1 induced ErbB3 and ErbB4 activation."
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"It will also be important to determine if molecular profiling of the primary tumor can predict which tumors are likely to increase the expression of EGFR and HER2 when treated with ER targeted therapy."
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"Interestingly, the selective estrogen receptor modulator (SERM) tamoxifen and ER antagonist ICI 182,780 both promote GPR30 dependent transactivation of the EGF receptor and subsequent MAPK activation."
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"Indeed, we found that activation of KISS1R in breast cancer cells lacking ERalpha induced epidermal growth factor receptor (EGFR) tyrosine kinase activity via a beta-arrestin2-dependent mechanism to s[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Preclinical studies with breast cancer cell lines and limited clinical data suggest that estrogen receptor (ER)-positive breast cancers initially inhibited by tamoxifen or by hormone deprivation can upregulate EGFR and HER2 signaling in order to bypass ER blockade."
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"It is also worth to mention that paradoxically the TPC population (defined as enriched for expression of ESA + CD44 + CD24 low cells), increases in response to estradiol treatment due to paracrine stimulation by non TPC ER positive cells mainly through EGFR [XREF_BIBR]."
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"By means of siRNA-mediated downregulation of CD44 expression and blocking experiments, we identified CD44v6 as a co-receptor for EGF- and ER-induced ErbB1 activation and for NRG1-induced ErbB3 and ErbB4 activation."
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"The ER-EGFR signaling axis appears to be reciprocal, with ER signaling promoting the activation of EGFR, and EGFR signaling promoting the actvation of ER."
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"These results suggest that the ER modulates EGFR and MAPK signalling efficiency in TAM-R cells possibly through the regulation of TGFalpha availability."
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"Primary and recurrent tumor samples were assessed by immunohistochemistry for expression of EGFR, Ki67, ER, PRA, PRB, activated (phosphorylated) EGFR (pEGFR) and ERK (pERK)."
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"Ligand bound receptors can initiate membrane proximal kinase cascades; for instance, ERalpha can activate Src-kinase leading to epidermal growth factor receptor (EGFR), mitogen activated protein kinase (MAPK) and phosphatidylinositol-3-kinase signaling [XREF_BIBR - XREF_BIBR], whereas PR can trigger Src-MAPK and Akt signaling [XREF_BIBR, XREF_BIBR]."
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"This ER-EGFR signaling axis appears to be reciprocal : ER signaling promotes the activation of EGFR, while EGFR signaling promotes the activation of ER."
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"Membrane ER and GPER activate epidermal growth factor receptor (EGFR) with downstream signaling through Ras and Raf and mitogen activated protein kinase (MAPK)."
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"However, in vitro evidence partly supported clinical studies and AR showed antiproliferative activity in only ER positive breast cancers but rather AR signaling promoted tumor growth in ER negative and human epidermal growth factor receptor 2 (HER2)-positive breast tumors [XREF_BIBR, XREF_BIBR]."
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"It is well documented that ERalpha indirectly activates EGFR through MMP-9- and MMP-2-catalyzed release of HB-EGF (Filardo et al., 2000; Razandi et al., 2003)."
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"Tamoxifen or estrogen bound membrane and cytoplasmic ER, through multiple interactions with signaling intermediate molecules such as Shc and modulator of nongenomic action of estrogen receptor (MNAR), can activate the EGFR and Her2 signaling pathway."
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"ERalpha can also directly activate the epidermal growth factor receptor (EGFR), causing activation of the MAPK and PI3K pathways XREF_BIBR, XREF_BIBR."
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"RX enhanced GLT-1 expression by the activation of multiple signaling pathways including ERK, EGFR, and CREB mediated by estrogen receptors (ERs) ER-alpha, ER-beta, and GPR30."
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"It is well documented that ERalpha indirectly activates EGFR through MMP-9- and MMP-2-catalyzed release of HB-EGF."
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"At least in some cases, it appears that ERalpha and GPER1 may function together to activate EGFR, since a physical interaction between ERalpha, GPER1 and EGFR is reported in endometrial and tamoxifen resistant breast cancer cells [XREF_BIBR]."
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"Treatment with β-estradiol increased secretion of VEGFA in NSCLC cells, which was largely mediated by ER activation of the EGFR."
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"It is well-documented that ERα indirectly activates EGFR through MMP-9- and MMP-2-catalyzed release of HB-EGF ( Filardo et al., 2000; Razandi et al., 2003 )."
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"In contrast, in ER positive tumors which did not overexpress erbB1 and/or erbB2, response rates were similar : 54% for letrozole versus 42% for tamoxifen (p = 0.078)."
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