Identification of Gab1 as a novel therapeutic target for hepatocellular carcinoma

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Recently, a better understanding of molecular pathogenesis regarding hepatocellular carcinoma (HCC), including growth factor or receptor Tyrosine Kinases (RTKs) signaling, has led to the development of the novel molecular target therapy. Grb2-associated binder Gab1 is a scaffolding docking adaptor that amplifies signals downstream of a broad range of growth factors/receptor tyrosine kinases, such as HGF/c-MET- or HB-EGF/EGFR- signaling pathways. Although these signals are implicated in liver carcinogenesis, the roles of Gab1 remain unclear. Here, we investigated the role of Gab1 in HCC and demonstrated that Gab1 regulates the proliferation of HCC cells in vitro and in vivo. Furthermore, hepatocyte-specific deletion of Gab1 in mice resulted in the enhanced liver fibrosis, which is the major cause of HCC in human. Together, our current results indicate the crucial role of Gab1 in hepatocarcinogenesis and that Gab1 could be a novel molecular target for HCC.