沉默Kif2a基因抑制舌癌侵袭转移及其机制研究

项目名称： 沉默Kif2a基因抑制舌癌侵袭转移及其机制研究

项目编号： No.81202142

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 王成勤

作者单位： 青岛大学

项目金额： 23万元

中文摘要： 细胞骨架在肿瘤细胞侵袭及转移过程中发挥重要的作用，微管是细胞骨架的重要组成部分，微管解聚蛋白（Kif2a）是一种驱动蛋白，能够通过解聚微管而影响细胞骨架。我们前期研究发现，Kif2a在舌鳞癌淋巴结转移灶中的表达显著强于原发灶，并与淋巴结有无转移成正相关； 此外，Kif2a基因沉默后，Rho/ROCK信号转导通路中Rho家族主要基因表达下调。由此推测，Kif2a除了自身解聚微管影响细胞骨架外，还可能通过Rho/ROCK信号转导通路调控细胞的侵袭及转移。本研究拟以Tca8113、SAS细胞及裸鼠移植瘤为研究对象，采用RNAi技术，从体内、体外两个层面探讨Kif2a对细胞侵袭转移能力的影响，同时通过研究Kif2a与Rho/ROCK信号转导通路的关系，探讨Kif2a调控细胞侵袭转移的分子机制。该研究将为以细胞骨架为靶点的抗肿瘤治疗提供新型靶分子及理论依据。

中文关键词： 微管解聚蛋白；增殖；转移；PI3K/Akt；Rho/ROCK

英文摘要： Cytoskeletal reorganizations play an important role in tumor cell invasion and metastasis. Microtubule depolymerase Kif2a is a member of the Kinesin-13 family, which may be involved in changing cytoskeleton of the cells by regulating the microtubules dynamics. Our previous studies showed that the expression of Kif2a was higher in lymph node metastasis than that in primary foci in tongue squamous cells carcinoma, and its expression was positively correlated with lymphatic metastasis. Moreover, the results of gene expression profile showed the gene-silence of Kif2a mediated by siRNA led to downregulation of the Rho family, which were the main components of Rho/ROCK signal pathway. Therefore we speculate that Kif2a might regulate cell invasion and metastasis via Rho/ROCK signal pathway besides depolymerizing microtubules. In this study, RNAi was used in both in vitro and in vivo experiments in order to observe the effects of Kif2a on the invasion and metastasis of Tca8113 and SAS cells. In addition, the mechanism of Kif2a regulating the invasion and metastasis of tumor cells were explored by analyzing the relationship between Kif2a and Rho/ROCK signal pathway. Therefore this research will provide a new target and theoretical basis for anti-cancer therapy.

英文关键词： Kif2a；proliferation；metastasis；PI3K/Akt；Rho/ROCK