迁移侵袭抑制蛋白 MIIP对有氧酵解介导的结肠肿瘤EMT的调控作用及机制研究

项目名称： 迁移侵袭抑制蛋白 MIIP对有氧酵解介导的结肠肿瘤EMT的调控作用及机制研究

项目编号： No.81502405

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 王秦豪

作者单位： 中国人民解放军第四军医大学

项目金额： 18万元

中文摘要： 上皮-间充质转化（EMT）和有氧糖酵解是肿瘤发生发展的标志性事件，其分子机制是肿瘤研究领域的热点和焦点。但结肠癌中哪些分子同时参与调节EMT和有氧酵解？二者之间是否存在相互调控？目前并不清楚。MIIP是合作课题组新近发现的抑癌基因，文献和我们前期研究表明：结肠癌中MIIP基因所在1p36.22缺失；MIIP抑制细胞增殖、侵袭和糖酵解；MIIP可负调控EMT相关因子Snail、Twist及糖代谢关键酶HK2、PFK2等。这些强烈提示MIIP可能作为EMT和有氧酵解的重要调节分子，发挥抑癌功能。基于此，本项目拟从细胞功能、分子机制、动物模型以及临床样本四个层次，明确MIIP在结肠癌有氧糖酵解和EMT中的作用；阐明MIIP调节有氧酵解的分子机制；探索MIIP协调调节有氧酵解和EMT的关键节点，并评估MIIP调控作用的临床意义。本研究将揭示MIIP新功能，并从代谢角度阐释结肠癌EMT调控机制。

中文关键词： 有氧酵解；EMT；MIIP；结肠癌；协同调控

英文摘要： Epithelial Mesenchymal Transition and aerobic glycolysis are the hallmarks in tumor initiation and development, the molecular mechanisms of these process are hotspots in cancer research. However, which molecule involved in the regulation of aerobic glycolysis and EMT simultaneously? Whether existed coordinate regulation between the two process? The answers were not yet clear. MIIP was a tumor suppresser gene that identified by our cooperation group recently, literatures and our preliminary work showed that MIIP gene location in chromosome 1p36.22 was deletion in colon caner; overexpression of MIIP inhibited cancer cell proliferation, metastasis and glycolysis; MIIP was a negative regulator of EMT transcriptional factor Snail, Twist and enzymes in glycolysis, such as HK2 and PFK2. These results strongly suggested that MIIP could be considered as a critical regulator in EMT and aerobic glycolysis. Therefore, we planned to investigate the function of MIIP in the aerobic glycolysis and EMT in colon cancer through cell effect, molecular mechanisms, mouse model and clinical samples; illuminate the molecular mechanisms of MIIP regulation in aerobic glycolysis; Explore the critical molecule node in MIIP-mediated aerobic glycolysis and EMT, and evaluate the clinical significance of MIIP. This study will indicate the new functions of MIIP, and explain the regulation mechanisms of EMT from the point of glucose metabolism in colon cancer.

英文关键词： aerobic glycolysis ;EMT;MIIP;colon cancer;coordinate regulation