Annexin A6蛋白的SUMO化修饰及其在细胞伪足形成中的作用

项目名称： Annexin A6蛋白的SUMO化修饰及其在细胞伪足形成中的作用

项目编号： No.31470810

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 梁淑芳

作者单位： 四川大学

项目金额： 80万元

中文摘要： 膜连蛋白A6 (Annexin A6, AnxA6)参与细胞粘附、迁移侵袭等膜相关的生物学过程。在我们前期已开展AnxA6蛋白表达与SUMO化修饰对伪足形成等研究的基础上，本课题重点探讨Annexin A6蛋白的SUMO化修饰在细胞伪足形成以及肿瘤细胞侵袭转移中的作用。即在不同恶性程度的肝癌细胞系-裸鼠皮下瘤模型-临床组织标本三个层次，分析不同恶性程度的肝癌细胞中AnxA6蛋白SUMO化修饰水平，并运用质谱技术、RNA干扰与定点突变等研究手段鉴定SUMO化修饰位点，研究不同程度的SUMO修饰对AnxA6参与的伪足形成的影响与生物学效应；进而在裸鼠整体动物模型和肝癌临床组织样本中验证该蛋白的SUMO修饰与成瘤能力、肿瘤侵袭转移的关系；从而明确AnxA6蛋白SUMO化修饰的细胞学功能及其在肿瘤转移中的作用。

中文关键词： SUMO化修饰；Annexin；A6蛋白；肝细胞癌；细胞伪足；侵袭转移

英文摘要： Annexin A6 (AnxA6) participates in a wide range of membrane associated biological processes, including cell adhesion, metastasis and invasion. Our previous studies have found that the SUMOylation level of AnxA6 is increased in highly metastatic cancer cells, and the sumoylated AnxA6 is probably involved in the formation of cell pseudopodia which is closely related with tumor invasion and metastasis. Based on these new findings on the sumoylated AnxA6, we will focus on discovering the biological roles of SUMOylated AnxA6 in the pseudopodia formation and tumor cell invasion and metastasis. Firstly the SUMOylation level of AnxA6 and its roles in cell pseudopodia formation will be analyzed in several hepatocellular carcinoma (HCC) cell lines with different malignancy degree. And the SUMOylation sites in AnxA6 will be identified by mass spectrometry technology, RNA interference and amino acid site-specific mutation. Furthermore, the effects of AnxA6 SUMOylation on tumor invasion and metastasis will be discovered based on the following studies on the nude mouse models with HCC and tissue specimens from HCC patients.

英文关键词： SUMOylation;Annexin A6;hepatocellular carcinoma;cell pseudopodia;cell invasion and metastasis