HCV感染是肝癌发生的重要危险因素，HCV与EMT（上皮样细胞向间质样细胞转化）的发生并参与HCC的转移和侵袭，是当前研究热点。课题组前期研究发现：HCV Core过表达细胞侵袭力增强，E-cadherin启动子区Snail结合增强，启动子活性受抑制、其表达下调，PI3K/Akt信号通路活化。由此我们提出“HCV Core协同 Snail调控E-cadherin表达，参与HCC转移”的科学假说。本研究拟通过HCV感染和Core过表达细胞模型、裸鼠肝癌转移模型及临床组织病理分析，检测HCV Core、Snail和 E-cadherin表达相关性，解析Core与Snail或组蛋白修饰酶形成复合物，调控E-cadherin表达；研究PI3K/Akt信号通路如何参与HCV Core诱导的EMT。本研究旨在探讨Core调控E-cadherin并参与HCC转移的机制，并为优化肝癌的防治策略提供新手段。

Hepatocelluar carcinoma (HCC) is the fifth most common cancer worldwide and ranks as the third leading cause of cancer-related death in humans. One of the most important risk factors for the development of HCC is chronic hepatitis C virus (HCV) infection. The oncogenic role of HCV core and its molecular mechanisms in HCV-induced hepatocarcinogenesis have not been clearly elucidated. Down-regulation of E-cadherin by transcriptional repressor Snail is associated with acquisition of metastatic potential. Although hepatitis C virus (HCV) core protein has been implicated in hepatocarcinogenesis, it is unclear if Snail involves in the dysregulation of E-cadherin induced by HCV core.. .Our preliminary data indicate that 1) HCV core effectively induced epithelial-mesenchymal transition (EMT) in hepatoma cells by repressing E-cadherin; 2) HCV core was shown to interact with Snail and enhanced its binding to E-box in the promoter region of E-cadherin, leading to the decreased E-cadherin promoter activity; 3) HCV core activates the Akt/GSK3β pathway to regulate Snail-dependent EMT...Based on our preliminary data, we hypothesized that HCV core could repress E-cadherin through the formation of the core-Snail-histone deacetylases (HDACs) transcriptional corepressor complex, resulting in EMT induction, leading to hepatoma cell metastasis. In this study, the effect of HCV core protein on the morphology and migration capacity of hepatoma cells was examined. HCV-infected primary human hepatocyte, HCV Core-transduced cells and HCV-related HCC tissue samples were used to investigate the molecular mechanism that HCV core induces E-cadherin repression and the role of Snail in HCV core-mediated invasiveness. Luciferase reporter and chromatin immunoprecipitation assays were used to assess the effect of Snail on transcriptional repression induced by HCV core. Xenograft tumor model was to determine the effect of Snail on HCV core-mediated invasiveness and metastasis. Our studies will provide new insights into the molecular mechanism underlying tumor invasion and metastasis in HCV-related HCC, and could potentially lead to novel therapeutic approaches for the treatment of metastatic HCC in patients with chronic HCV infection.