UNLABELLED: The mitogen-inducible gene-6 (mig-6) is a multi-adaptor protein implicated in the regulation of the HER family of receptor tyrosine kinases. We have reported recently that mig-6 is a negative regulator of epidermal growth factor receptor (EGFR)-dependent skin morphogenesis and tumor formation in vivo. In the liver, ablation of mig-6 leads to an increase in EGFR protein levels, suggesting that mig-6 is a negative regulator of EGFR function. In line with this observation, primary hepatocytes isolated from mig-6 knockout and wild-type control mice display sustained mitogenic signaling in response to EGF. In order to explore the role of mig-6 in the liver in vivo, we analyzed liver regeneration in mig-6 knockout and wild-type control mice. Interestingly, mig-6 knockout mice display enhanced hepatocyte proliferation in the initial phases after partial hepatectomy. This phenotype correlates with activation of endogenous EGFR signaling, predominantly through the protein kinase B pathway. In addition, mig-6 is an endogenous inhibitor of EGFR signaling and EGF-induced tumor cell migration in human liver cancer cell lines. Moreover, mig-6 is down-regulated in human hepatocellular carcinoma and this correlates with increased EGFR expression. CONCLUSION: Our data implicate mig-6 as a regulator of EGFR activity in hepatocytes and as a suppressor of EGFR signaling in human liver cancer.
UNLABELLED: The mitogen-inducible gene-6 (mig-6) is a multi-adaptor protein implicated in the regulation of the HER family of receptor tyrosine kinases. We have reported recently that mig-6 is a negative regulator of epidermal growth factor receptor (EGFR)-dependent skin morphogenesis and tumor formation in vivo. In the liver, ablation of mig-6 leads to an increase in EGFR protein levels, suggesting that mig-6 is a negative regulator of EGFR function. In line with this observation, primary hepatocytes isolated from mig-6 knockout and wild-type control mice display sustained mitogenic signaling in response to EGF. In order to explore the role of mig-6 in the liver in vivo, we analyzed liver regeneration in mig-6 knockout and wild-type control mice. Interestingly, mig-6 knockout mice display enhanced hepatocyte proliferation in the initial phases after partial hepatectomy. This phenotype correlates with activation of endogenous EGFR signaling, predominantly through the protein kinase B pathway. In addition, mig-6 is an endogenous inhibitor of EGFR signaling and EGF-induced tumor cell migration in humanliver cancer cell lines. Moreover, mig-6 is down-regulated in humanhepatocellular carcinoma and this correlates with increased EGFR expression. CONCLUSION: Our data implicate mig-6 as a regulator of EGFR activity in hepatocytes and as a suppressor of EGFR signaling in humanliver cancer.
Authors: C Hermanns; V Hampl; K Holzer; A Aigner; J Penkava; N Frank; D E Martin; K C Maier; N Waldburger; S Roessler; M Goppelt-Struebe; I Akrap; A Thavamani; S Singer; A Nordheim; T Gudermann; S Muehlich Journal: Oncogene Date: 2017-01-23 Impact factor: 9.867
Authors: E Scott Colvin; Hong-Yun Ma; Yi-Chun Chen; Angelina M Hernandez; Patrick T Fueger Journal: Endocrinology Date: 2013-02-05 Impact factor: 4.736