Tiam1基因在肝癌转移中的作用及其网络调控机制

项目名称： Tiam1基因在肝癌转移中的作用及其网络调控机制

项目编号： No.30801380

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 丁轶

作者单位： 南方医科大学

项目金额： 20万元

中文摘要： 我们通过免疫组化检测，结合临床随访资料进行统计分析，发现Tiam1高表达是判断肝癌患者预后不良的一个重要因素，且Tiam1表达水平与肝癌的转移密切相关。利用基因稳定转染和RNA干扰技术分别处理同一遗传背景、不同转移潜能的两种肝癌细胞株（MHCC97L、HCCLM6），经体内外实验研究证明Tiam1基因能促进肝癌细胞的增殖、侵袭和转移能力。采用酵母双杂交、免疫共沉淀、共定位方法和生物信息学分析，筛选并鉴定出与Tiam1相互作用的蛋白，进而确定Tiam1基因在肝癌转移中的作用，初步阐明Tiam1在肝癌转移中的网络调控机制，为抗肝癌转移靶向治疗提供理论依据。

中文关键词： Tiam1；肿瘤转移；肝癌；信号转导

英文摘要： Tiam1 expression level was detected by immunohistochemistry in 152 cases of hepatocellular carcinoma (HCC) tissues, and consequently analyzed to be significantly associated with HCC metastasis, which showed that patients with Tiam1 overexpression had a significantly shorter overall survival time than those with Tiam1 downexpression. In this study, we investigated, both in vitro an in vivo, the effect of Tiam1 gene on proliferation, adhesion, migration and invasion in HCC through genetically stable transfection and RNA interference, and demonstrated that Tiam1 may contribute to the proliferation, migration and invasion of HCC cells. Furthermore, we also screened and identified Tiam1-interacted protein by using yeast two-hybrid, immunoprecipitation, co-localization methods, and bioinformatics analysis. We think all of our study would help us well to explore the possible mechanism of Tiam1 and its signal transduction in HCC metastasis, thus providing a theoretical basis for HCC targeted therapy.

英文关键词： Tiam1;tumor metastasis;hepatocellular carcinoma;signal transduction