p53靶基因Rap2B对肿瘤细胞骨架的调节作用及其分子机制

We identified Rap2B by analyzing a p53 target gene expression microarray database, but little is known about the role of Rap2B in tumor development and tumorigenesis. Our previous experimental results suggest that, Rap2B has a central role in regulating cellular migration, and proposed the mechanism of Rap2B exerting its pro-migration function through its interaction with cytoskeletal proteins.. In this project, at cellular level, we will study the effect of Rap2B in the polymerization and depolymerization of microtubule and actin filaments, and the regulation of Rap2B to cytoskeletal proteins such as Cdc42，Rac，Rho; At molecular level, we will study whether Rap2B can regulate tumor cytoskeleton through its downstream specific effect factors TNIK and PARG, and related mechanism research. We expect our research will uncover the role of Rap2B in tumor development, and will offer another point for potential cancer therapeutic intervention.

申请者利用Mdm2 微阵列芯片筛选p53靶基因时发现Rap2B基因。该基因在肿瘤发生发展中的作用未见报道。预实验结果提示，Rap2B可能通过调节肿瘤细胞骨架蛋白，改变细胞形态，从而促进细胞迁移。.有鉴于此，本项目将在细胞水平研究Rap2B对细胞微管、微丝的聚合及解聚作用的影响，以及对细胞骨架蛋白（Cdc42，Rac，Rho）的调节作用；在分子水平研究Rap2B是否通过其下游特异性效应因子TNIK与PARG调节细胞骨架，及其具体机制。以期揭示Rap2B与肿瘤发生发展的关系，为筛选抗肿瘤靶点提供理论依据。

申请者前期利用Mdm2 微阵列芯片筛选出p53下游靶基因Rap2B。该基因在肿瘤发生发展中的作用未见报道。预实验结果提示，Rap2B可能通过调节肿瘤细胞骨架蛋白，改变细胞形态，从而促进细胞迁移。本课题主要研究Rap2B在调节肿瘤细胞形态及细胞迁移中的作用及其分子机制。其具体作用及其机制如下：. 1、Rap2B能通过F-actin调节肿瘤细胞骨架重组从而抑制肿瘤细胞铺展；2、Rap2B在肾癌细胞及组织中高表达，能通过上调MMP-2的蛋白表达及其酶活性，从而促进人肾癌细胞的迁移及侵袭；3、Rap2B在乳腺癌细胞中高表达，能通过上调乳腺癌细胞内的钙离子及ERK磷酸化水平，从而促进人乳腺癌细胞的增殖、迁移及侵袭。本课题的研究初步揭示了Rap2B在肿瘤发生发展中的重要性，为筛选抗肿瘤靶点提供理论依据。