TUFM调控EMT及肺癌浸润转移的作用及其机理研究

项目名称： TUFM调控EMT及肺癌浸润转移的作用及其机理研究

项目编号： No.81472603

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 宋建国

作者单位： 中国科学院上海生命科学研究院

项目金额： 80万元

中文摘要： 本项目旨在通过研究TUFM（线粒体EF-Tu)对EMT的调控及其在肺癌细胞生长转移中的作用，了解EMT和线粒体功能的关联性以及对肺癌发展影响的问题。线粒体翻译延长因子TUFM参与线粒体DNA编码的氨基酸肽链的延伸起始调控，是线粒体DNA翻译表达的限速因子，其分子水平的异常可以深刻地影响线粒体基因编码蛋白的表达和线粒体的功能。研究表明，在癌症的发生发展中常伴有线粒体功能的异常和通过细胞的上皮-间质转化（EMT）而出现癌浸润转移的现象，但两者之间的关系如何，线粒体基因编码蛋白与EMT有何关联还很不清楚。因此，本项目研究内容具有突出的新颖性和重要科学意义，有助于了解线粒体编码基因和线粒体功能异常调节与EMT的关联及其在癌细胞行为和癌肿生长浸润转移中的作用问题。

中文关键词： C05_气管；支气管；肺肿瘤；细胞转分化；肿瘤转移；线粒体；细胞色素氧化酶C

英文摘要： Through investigating TUFM-mediated regulation of EMT and the effect TUFM on the growth and metastasis of lung cancer cells, this project aimed to understand the relevance of EMT and the mitochondria function and its impact on cancer progression. Mitochondria is not only an organelle for cellular energy generation, it is also an important site for the production of free radicals and the regulation of cell metabolism and programmed death. It has been demonstrated that abnormal mitochondrial functions and EMT-mediated tumor invasion and metastasis are often associated with the development and progression of cancers. However, the relationship between these two events and linkage between EMT and mitochondrial gene-encoded proteins are very poorly understood. TUFM, a mitochondria translational elongation factor that is implicated in the control of initiation of the elongation of amino acid peptide encoded by mitochondrial DNA, is a rate-limiting factor for the translational expression of mitochondrial DNA. The abnormal alteration of TUFM level will significantly influence the mitochondrial function and its gene expression. Based on this background, the proposal is aimed at determining the effects of TUFM levels on the epithelial/mesenchymal properties of cancer cells and its role in the induction of EMT, identifying the impact and its molecular mechanism of TUFM-mediated regulation of EMT on lung cancer growth, invasion, and metastasis.

英文关键词： lung cancer;EMT;Tumor metastasis;Mitochondria;COX