EGFR signal transactivation in cancer cells

Fischer, Oliver M.; Hart, Stefan; Gschwind, Andreas; Ullrich, Axel

doi:10.1042/bst0311203

Cited by 362 publications

(276 citation statements)

References 48 publications

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“…The transactivation of EGFR by G-protein-coupled receptors is recognized as an important signaling mechanism in the regulation of complex biological processes such as cancer development (28). Recently, other studies have assessed EGFR involvement in cardioprotection mediated by adenosine receptors (ARs).…”

Section: Discussionmentioning

confidence: 99%

Potential prognostic biomarker CD73 regulates epidermal growth factor receptor expression in human breast cancer

Zhi

Wang

et al. 2012

IUBMB Life

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SummaryCD73, an ecto-enzyme overexpressed in breast-cancer cells, catalyzes the dephosphorylation of adenosine monophosphates into adenosine. Anti-CD73 slows breast cancer growth and its spread both in vivo and in vitro. In this study, we investigated the relation of CD73 to epidermal growth factor receptor (EGFR) expression using tissue array and breast cancer cell lines. We found that CD73 expression correlated positively to EGFR expression in vivo (n 5 80, r 5 0.425, P \ 0.01) and in vitro. EGFR expression can be decreased by suppressing CD73 with an inhibitor or small shRNA, and this effect was reversed by adenosine and NECA (adenosine A2 receptor agonist), which suggested that adenosine is involved in EGFR expression regulated by CD73 (P \ 0.01). We also showed that CD73 regulates EGFR phosphorylation by Src (P \ 0.01). By transcription factor (TF) assay, CD73 was found to regulate some associated TFs activity such as PPARc, which mediates EGFR expression, although whether PPARc mediates the effect of CD73 on EGFR expression needs further study. The KaplanMeier recurrence-free survival curves for CD73 were also plotted in www.kmplot.com. The curves show that CD73 expression separates the cases into significantly different prognostic groups among the estrogen receptor-negative cancers (P \ 0.01). Our results suggest that CD73 may be a potential prognostic biomarker associated with coexpression of EGFR in human breast cancer.2012 IUBMB IUBMB Life, 64(11): 911-920, 2012

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Section: Discussionmentioning

confidence: 99%

Potential prognostic biomarker CD73 regulates epidermal growth factor receptor expression in human breast cancer

Zhi

Wang

et al. 2012

IUBMB Life

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“…In general, G-protein -coupled receptors can transactivate HER family members either by ectodomain shedding of membrane-bound HER family receptor ligands by members of the ADAM (a Disintegrin and metalloprotease) family of proteases (5) or by intracellular phosphorylation of HER family members involving Src kinase (6). In breast cancer cells, CXCL12/CXCR4 interaction activates HER2 in a Src kinasedependent mechanism (7).…”

Section: Introductionmentioning

confidence: 99%

CXCL12/CXCR4 Transactivates HER2 in Lipid Rafts of Prostate Cancer Cells and Promotes Growth of Metastatic Deposits in Bone

Chinni

Yamamoto

Dong

et al. 2008

Molecular Cancer Research

120

102

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Chemokines and their receptors function in migration and homing of cells to target tissues. Recent evidence suggests that cancer cells use a chemokine receptor axis for metastasis formation at secondary sites. Previously, we showed that binding of the chemokine CXCL12 to its receptor CXCR4 mediated signaling events resulting in matrix metalloproteinase-9 expression in prostate cancer bone metastasis. A variety of methods, including lipid raft isolation, stable overexpression of CXCR4, cellular adhesion, invasion assays, and the severe combined immunodeficient -human bone tumor growth model were used. We found that (a) CXCR4 and HER2 coexist in lipid rafts of prostate cancer cells; (b) the CXCL12/CXCR4 axis results in transactivation of the HER2 receptor in lipid rafts of prostate cancer cells; (c) Src kinase mediates CXCL12/CXCR4 transactivation of HER2 in prostate cancer cells; (d) a pan-HER inhibitor desensitizes CXCR4-induced transactivation and subsequent matrix metalloproteinase-9 secretion and invasion; (e) lipid raft -disrupting agents inhibited raft-associated CXCL12/CXCR4 transactivation of the HER2 and cellular invasion; (f) overexpression of CXCR4 in prostate cancer cells leads to increased HER2 phosphorylation and migratory properties of prostate cancer cells; and (g) CXCR4 overexpression enhances bone tumor growth and osteolysis. These data suggest that lipid rafts on the cell membrane are the key site for CXCL12/CXCR4 -induced HER2 receptor transactivation. This transactivation contributes to enhanced invasive signals and metastatic growth in the bone microenvironment.

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“…Epidermal growth factor receptor transactivation by ligandindependent intracellular signalling mechanisms and metalloprotease-mediated processing of the EGF-like ligands has been investigated in the last couple of years (Fischer et al, 2003). Recently, the transactivation of EGFR by TNF-a-induced metalloprotease processing of TGF-a has been demonstrated in hepatocytes and mammary epithelial cells (Argast et al, 2004;Chen et al, 2004).…”

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confidence: 99%

Selective inhibition of TNF-α-induced activation of mitogen-activated protein kinases and metastatic activities by gefitinib

et al. 2005

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We have reported that the selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib ('Iressa', ZD1839), suppressed intrahepatic metastasis of hepatocellular carcinoma CBO140C12 cells. In this study, we focused on the tumour necrosis factor-a (TNF-a) signalling pathways. Real-time reverse transcription -polymerase chain reaction showed that TNF-a mRNA was expressed in large quantities in the implanted tumour. Gefitinib inhibited EGF-but not hepatocyte growth factor (HGF)-induced activation of mitogen-activated protein kinase (MAPK) cascades, suggesting selectivity of the inhibitor. However, gefitinib inhibited the TNF-a-induced activation of MAPKs and Akt. In addition, TNF-a-induced metastatic properties including adhesion to fibronectin, mRNA expression of integrin av, production of matrix metalloproteinase-9 and invasion were inhibited by gefitinib without affecting cell proliferation. Furthermore, the TNF-a-induced responses except for NF-kB activation were blocked by metalloprotease inhibitors, suggesting that gefitinib inhibited the transactivation of EGFR induced by TNF-a. These results suggest that the TNF-a signalling pathway is a possible target of gefitinib in suppressing the intrahepatic metastasis of hepatocellular carcinoma.

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EGFR signal transactivation in cancer cells

Cited by 362 publications

References 48 publications

Potential prognostic biomarker CD73 regulates epidermal growth factor receptor expression in human breast cancer

Potential prognostic biomarker CD73 regulates epidermal growth factor receptor expression in human breast cancer

CXCL12/CXCR4 Transactivates HER2 in Lipid Rafts of Prostate Cancer Cells and Promotes Growth of Metastatic Deposits in Bone

Selective inhibition of TNF-α-induced activation of mitogen-activated protein kinases and metastatic activities by gefitinib

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