Lgr5促进肝癌细胞上皮间质转化的分子机制

项目名称： Lgr5促进肝癌细胞上皮间质转化的分子机制

项目编号： No.81472268

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘志苏

作者单位： 武汉大学

项目金额： 72万元

中文摘要： 肝癌的侵袭转移和术后复发是肝癌患者死亡的主要原因。上皮-间质转化(EMT)与肝癌复发及转移密切相关, 已成为当前生命科学研究的热点。多种信号转导通路参与了肿瘤细胞的EMT过程,其中Wnt/β-catenin信号通路尤为引起人们的关注。作为Wnt 信号通路的重要靶基因，G-蛋白偶联受体5(Lgr5)，在体内细胞信号转导和代谢调节等方面发挥着重要作用。我们前期工作提示，LGR5可能是通过Wnt/β-catenin信号传导通路介导原发性肝癌的上皮间质转化。为探求其具体分子机制，我们将从表观遗传的角度探讨研究Lgr5基因的表达调控机制；运用蛋白组学技术筛选与Lgr5相关的侵袭转移蛋白；并将重点研究Lgr5对β-catenin的表达调控机制；最后采用酵母双杂交鉴定Lgr5与靶蛋白相互作用结构域。以其明确Lgr5在肝癌细胞侵袭转移过程中是否起关键作用，为肝癌治疗提供新的靶位点。

中文关键词： Lgr5；肝癌；上皮间质转化；转移

英文摘要： The depth of tumor invasion, metastasis, and postoperative relapse are universal and continues to be the main cause of late deaths in patients with liver cancer.Epithelial - mesenchymal transition (EMT) is closely associated with frequent postoperative recurrence and poor survival in patients with hepatocellular carcinoma. The most recent research indicates that EMT is currently a hot topic of among liver cancer researchers. Signaling pathways have been implicated in EMT regulating important processes during the development of hepatocellular carcinoma including Wnt/ -catenin signaling pathway. G- protein coupled receptor 5 (Lgr5),as an important target gene of Wnt signal pathway,is playing an important role in metabolic regulation and signal transduction processes within cells. Our previous work suggested that Lgr5 could promote EMT and enhance liver cancer recurrence involving Wnt/β -catenin signal transduction pathway.However, the molecular mechanism underlying of Lgr5-induced EMT was not clear. Here, we will explore the possible epigenetic mechanisms of Lgr5 gene aberrant expression in liver cancer and screen invasion/metastasis-associated gene interacts with LGR5 to stimulate tumor recurrence on a genome-wide scale. Then we will focus on the the molecular mechanism of how LGR5 regulate the expression of β-catenin. At last,we will identify the interaction domains of Lgr5 and targeted protein by using two-hybrid yeast technique. In a word, we want to know whether Lgr5 is playing a key role or not in invasion and metastasis of hepatocellular carcinoma and provide a new target site for the treatment of liver cancer.

英文关键词： Lgr5;liver cancer;EMT;metastasis