MACC1调控葡萄糖代谢抑制胃癌细胞衰老的机制研究

项目名称： MACC1调控葡萄糖代谢抑制胃癌细胞衰老的机制研究

项目编号： No.81472317

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： 石敏

作者单位： 南方医科大学

项目金额： 55万元

中文摘要： 已知代谢应激能诱发机体细胞衰老，而肿瘤细胞却能以独特的葡萄糖代谢方式（Warburg效应）抵抗衰老。近年，许多癌基因被证实参与肿瘤细胞代谢和衰老调控。结肠癌转移相关基因-1（MACC1）是新近发现的癌基因，我们首次报道了MACC1能影响胃癌的细胞周期和活力，并影响患者预后。但尚不知：MACC1与肿瘤代谢、衰老的关系是什么？我们近期发现代谢应激能够上调胃癌细胞MACC1表达，MACC1过表达能增强葡萄糖代谢并抑制细胞衰老，提示MACC1可能在抵抗胃癌细胞衰老和代谢调控中发挥重要作用。因此我们假设：代谢应激代偿性地使胃癌细胞MACC1升高，MACC1通过Warburg效应抵抗其衰老。本项目拟借助代谢状态检测、细胞功能实验及分子生物学实验等手段，从临床、动物、细胞和分子四个层次展开研究，阐明MACC1与胃癌细胞代谢调控及抗衰老调控的关系。

中文关键词： C07_胃肿瘤；MACC1；细胞衰老；Warburg效应；代谢应激

英文摘要： It is known that celluar senescence can be induced by metabolic stress, while cancer cells usually resist against senescence by adopting a unique metabolic manner (i.e. Warburg effect). Recently, more and more oncogenes are proved to take part in cancer cell metabolism and senescence regulation. Metastasis-associated in colon cancer-1 (MACC1) is a newly identified oncogene, and we first reported that MACC1 regulated the cell-cycle and ensured the viability of gastric cancer (GC) cells. Currently, the relation between MACC1 and tumor metabolism as well as cancer senescence resistance remains unknown. Our latest experiments on GC discovered that metabolic stress increased MACC1 expression, and that MACC1 upregulation enhanced glucose metabolism and suppressed GC cell senescence. These suggested that MACC1 might play a significant role in regulating GC glucose metabolism and senescence-resistance. Accordingly, we hypothesize that MACC1 compensatory upregulation helps GC cells resist against metabolic stress-induced senescence by promoting Warburg effect. Current project will be carried out by means of metabolic status assay, cellular functional experiments, and molecular biological experiments at clinical, animal, cellular, and molecular levels. The results of this study will clarify the relationship among MACC1, Warburg effect and senescence resistance.

英文关键词： gastric cancer;MACC1;cell senescence;Warburg effect;metabolic stress