肝癌是最常见的恶性肿瘤之一。YAP及其同源蛋白TAZ为HIPPO抑癌通路下游转录共激活因子。研究表明，YAP和TAZ共同参与了原癌基因c-MYC对肝癌进展的调控，然而此过程中YAP和TAZ在功能上的差异性尚未阐明。我们前期研究表明，c-MYC阳性肝癌临床标本中TAZ阳性率较YAP阳性率更高。c-MYC诱导的小鼠肝癌组织中TAZ上调较YAP更为显著。在c-MYC激活诱导肝癌形成的起始阶段敲除TAZ能完全阻滞肿瘤形成，而敲除YAP仅能延缓肿瘤进展。因此我们提出假设：c-MYC诱导的肝癌形成过程中YAP和TAZ的作用机制不同，且TAZ发挥更为关键的作用。本课题拟结合动物模型和细胞实验等方法，以YAP和TAZ为主要研究对象，在c-MYC诱导肝癌形成的起始和进展阶段，分别阐明YAP和TAZ可能的作用及分子机制，为探索开发以精准医疗为导向的新型肝癌治疗方法提供理论依据。

Liver cancer is one of the most common malignant tumors. YAP and its homologous protein TAZ are transcriptional coactivators downstream of the HIPPO tumor suppressor pathway. Studies have shown that YAP and TAZ are coordinately involved in the proto-oncogene c-MYC induced liver cancer. However, the differential role of YAP and TAZ has not been elucidated in the context of c-MYC activation induced liver cancer. Our preliminary data showed that the TAZ positive staining rate was higher than that of YAP in c-MYC positive HCC samples. c-MYC induced TAZ upregulation in mouse liver cancer tissue was more significant than YAP. Strikingly, liver specific depletion of TAZ completely blocked the formation of c-MYC liver cancer while depletion of YAP in mouse liver moderately delayed the tumor progression. Therefore, we hypothesize that mechanisms in regulating YAP and TAZ are distinct during c-MYC-induced liver cancer formation and HIPPO downstream effector TAZ has a more critical role than YAP. In our present proposal, we aim to clarify the role and mechanisms of YAP and TAZ during c-MYC-induced liver cancer initiation and progression, in vivo as well as in vitro. Our study will provide strong evidence for developing new methods of precision medicine-oriented liver cancer treatment.