肝细胞癌（肝癌）是临床最常见的恶性肿瘤之一，其发病机制仍有待进一步阐明。前期我们发现PDLIM1通过稳定E-cadherin/β-catenin复合物阻抑结直肠癌转移（Cancer Res. 2016;76:1122-34），后续研究发现PDLIM1在肝癌中表达显著下调。通过筛选PDLIM1相互作用蛋白，我们发现PDLIM1与Hippo信号通路的关键调控因子Tead4相互作用，提示PDLIM1可能通过Hippo通路调控肝癌发生。在此基础上，拟结合细胞与动物模型，明确PDLIM1与Tead4在肝癌发生过程中的生物学功能；阐明PDLIM1与Tead4相互作用的位点和机制；扩大肝癌临床样本量，明确 PDLIM1与Tead4在肝癌发生过程中的病理学意义。通过本项目的实施，有望阐明 PDLIM1/Tead4在肝癌发生中的生物学功能，为后续转化医学研究奠定基础。

Hepatocellular carcinoma (HCC) is one of the most common cancer worldwide. The mechanisms underlying HCC tumorigenesis remain poorly understood. In the previous study, we have demonstrated that PDLIM1 could stabilize the E-cadherin/β-catenin complex to prevent epithelial-mesenchymal transition and metastatic potential of colorectal cancer cells. Recently, we found that PDLIM1 was down-regulated in HCC, and Tead4, a key regulator of Hippo pathway, was identified as a potential PDLIM1-interacting protein, suggesting that PDLIM1 might inhibit hepatocarcinogenesis via regulation of Hippo pathway. In this project, the pathological significance of both PDLIM1 and Tead4 will be evaluated. Additionally, we will examine the molecular mechanism and biological function of PDLIM1-regulated Hippo/Tead pathway in hepatocarcinogenesis both in vitro and in vivo. Our study will lead to elucidation of the functional role of PDLIM1 in HCC development.