线粒体TRAP1分子介导Ago2蛋白表达在肠癌转移中的作用机制

项目名称： 线粒体TRAP1分子介导Ago2蛋白表达在肠癌转移中的作用机制

项目编号： No.81460446

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 吕元明

作者单位： 桂林医学院

项目金额： 47万元

中文摘要： 目前Hsp90分子抑制剂作为抗肿瘤药物已进入临床试验，但试验发现肿瘤细胞转移无法完全得到抑制。近年来研究表明，肿瘤细胞线粒体中，Hsp90分子相关肿瘤坏死因子受体蛋白TRAP1被认为是肿瘤细胞转移无法完全得到抑制的原因。我们前期研究发现TRAP1分子在转移性肠癌中存在表达差异，TRAP1分子与miRNA结合蛋白Ago2发生免疫共沉淀，并影响肠癌细胞的粘附、迁移能力，提示TRAP1分子可能是影响肿瘤细胞转移的重要因素，但其具体的作用机制尚不清楚。本课题拟选择两种不同转移潜能肠癌细胞，SW480/SW620，通过干预细胞TRAP1表达等方法，观察TRAP1对肠癌细胞转移的生物学行为的影响；探讨TRAP1分子表达及靶基因转录后与Ago2分子的相互作用；并研究TRAP1对EMT转移相关分子的作用，阐明TRAP1分子对肿瘤细胞转移的作用机制及途径，为今后临床有效治疗肠癌寻找相应的治疗靶点提供依据。

中文关键词： C08_结；直肠肿瘤；肿瘤转移；TRAP1；细胞侵袭

英文摘要： While previous research has demonstrated that a class of proteins known as molecular chaperones promote tumor cell survival, the specific way in which the proteins achieve this has not been well understood. And although inhibitors of a specific chaperone know as heat shock protein 90 (Hsp90) have been studied for the treatment of cancer, for example, 17-AAG, a small structure of inhibitor of Hsp90, has enter the trial, progress has been questionable. Notably, researcher found a very abundant pool of TRAP1 ( Hsp90-related molecule) in the mitochondrial of tumor cells. This mitochondrial accumulation of TRAP1 as a critical adaptive mechanism that makes cancer cells less susceptible to the unfavorable environment of tumors, and to various anticancer agents. The sub-cellular location of Hsp90 and TRAP1 in the mitochondrial also answers the question as to why the current Hsp90 inhibitors which do not penetrate the mitochondrial are not as effective as hoped in the clinic. In current study, we have collected two types of different metastasis potential colon cell line, SW620/SW480, for the further studying the effect of mitochondrial TRAP1 on the colon cancer metastasis. Based on our preliminary research, combining RNAi technique in colon cancer cell lines and other proteomics techinques were applied for studying the correlation between TRAP1 and key components of the miRNA, Argonaute2(Ago2), in which we try to clarify the possible mechanism of colon cacner metastasis.

英文关键词： Colorectal cancer;Cancer metastasis;TRAP1;Cell Migration