Identification of Gab1 as a novel therapeutic target for hepatocellular carcinoma

最近，对肝细胞癌（HCC）的分子发病机制，包括生长因子或受体酪氨酸激酶（RTKs）信号传导的更好理解，导致了新的分子靶向治疗的发展。grb2相关结合物Gab1是一种支架对接适配器，可放大多种生长因子/受体酪氨酸激酶的下游信号，如HGF/c-MET-或HB-EGF/EGFR-信号通路。尽管这些信号与肝癌发生有关，但Gab1的作用尚不清楚。在这里，我们研究了Gab1在HCC中的作用，并证明了Gab1在体外和体内调节HCC细胞的增殖。此外，小鼠肝细胞特异性缺失Gab1导致肝纤维化增强，这是人类HCC的主要原因。总之，我们目前的结果表明Gab1在肝癌发生中的关键作用，并且Gab1可能是HCC的新分子靶点。

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.