The role of FAK in hepatocarcinogenesis

描述（由申请人提供）：本申请的中心焦点是了解局灶黏附激酶（FAK）在肝癌中的作用。肝细胞癌（HCC）是美国增长最快的癌症。目前，HCC的潜在机制尚不完全清楚。了解驱动或介导HCC发展的分子信号通路对于确定预防或治疗HCC的新治疗靶点非常重要。FAK已被证明在几种组织的肿瘤发生和癌症进展中发挥重要作用，然而，由于缺乏体内研究，FAK在肝癌中的作用仍然难以捉摸。目前，几种FAK抑制剂正被用作早期临床试验中有前景的抗实体肿瘤药物。由于大多数药物代谢发生在肝脏，因此了解FAK对肝脏的抑制作用至关重要。我们发现了FAK的删除

DESCRIPTION (provided by applicant): The central focus of this application is to understand the role of focal adhesion kinase (FAK) in liver cancer. Hepatocellular carcinoma (HCC) is the most rapidly increasing cancer in the United States. Currently, the underlying mechanisms of HCC are not fully known. Understanding the molecular signaling pathways that drive or mediate the development of HCC is important for identifying novel therapeutic targets for preventing or treating HCC. FAK has been shown to play an important role in tumorigenesis and cancer progression in several tissues, however, the role of FAK in liver cancer remains elusive due to the lack of in vivo studies. Currently, several FAK inhibitors are being used as promising anti-solid tumor agents in early-phase clinical trials. As most drug metabolism occurs in the liver, it s critical to understand the effect of inhibition of FAK on liver. We have found that deletion of FAK promotes steatohepatitis, hepatic fibrosis and hepatic proliferation in hepatocyte-specific Phosphatase and Tensin Homolog (PTEN)-deficient mice. As steatohepatitis, hepatic fibrosis and enhanced hepatic proliferation are thought to promote liver cancer, we propose that deletion of FAK in liver promotes hepatocarcinogenesis in hepatocyte- specific PTEN-deficient mice model. We then intend to understand the role of FAK in hepatocarcinogenesis in which activation of FAK is not due to loss of PTEN. To achieve this goal, we plan to use a carcinogen, diethylnitrosamine(DEN)-induced HCC mouse model in which activation of FAK is not due to loss of PTEN. This study will provide new insights into the role of FAK in liver cancer, which is important for treating either liver cancer or other types of cancers by targeting FAK.