MPP3调控肝癌细胞迁移和侵袭的分子机制研究

项目名称： MPP3调控肝癌细胞迁移和侵袭的分子机制研究

项目编号： No.81502106

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 马海洁

作者单位： 温州医科大学

项目金额： 18万元

中文摘要： 新近研究表明膜结合鸟苷酸激酶（MAGUK）家族作为细胞内支架蛋白参与调控癌症的发生和发展，但其在肝癌中的作用未知。我们的前期研究在国家科技重大专项基金（2008ZX10002-021）的支持下，首次发现MAGUK家族成员棕榈酸酰化膜蛋白3（MPP3）在高转移潜能肝癌细胞株和肝癌组织中均显著性上调，且其过表达与肝癌患者预后差有关，并进一步证实MPP3促进肝癌细胞的迁移和侵袭，但其分子机制未明。我们的后续研究发现MPP3能与细胞周期素依赖蛋白激酶5（Cdk5）外源互作且在体外能被Cdk5磷酸化。结合文献检索和现有研究基础，我们提出假设：Cdk5磷酸化MPP3调控肝癌细胞的迁移和侵袭。本研究将延续前一课题，进一步揭示MPP3调控肝癌细胞迁移和侵袭的分子机制。通过以上机制的研究，为阐明肝癌侵袭、转移机理，寻找治疗肝癌的转移与复发的分子靶标提供重要理论依据。

中文关键词： 肝细胞癌；磷酸化；MPP3；Cdk5；侵袭

英文摘要： It has been demonstrated that membrane-associated guanylate kinase (MAGUK) family participate in the regulation of development of cancer in recent studies, but their roles in hepatocellular carcinoma (HCC) remain unclear. Our previous study ,supported by the National Key Sci-Tech Special Project of China （2008ZX10002-021）,has shown that membrane palmitoylated protein 3(MPP3), a member of MAGUK family ,is significantly up-regulated in HCC cell lines of high metastatic potential and HCC tissues ,and the overexpression of MPP3 correlated with poor prognosis in patients with HCC. Furthermore, we demonstrated that MPP3 promotes HCC cell migration and invasion. However, its molecular mechanism has not elucidated yet. In our follow-up study, we found MPP3 interacting with cyclin-dependent kinase 5(Cdk5) could be phosphorylated by Cdk5.In according to our precious work as well as literature research, we propose that MPP3 phosphorylation by Cdk5 regulates HCC cell migration and invasion,which will extend the finding of our precious work and unfold the molecular mechanism of MPP3 in regulation of HCC cell migration and invasion. By means of this study, it will provide important theoretical basis for elucidating the mechanism of invasion and metastasis and finding therapeutic targets of anti-metastasis and relapse of HCC.

英文关键词： hepatocellular carcinoma;phosphorylation;MPP3;Cdk5;invasion