HPIP在肿瘤细胞糖代谢中的功能及其调控机制

项目名称： HPIP在肿瘤细胞糖代谢中的功能及其调控机制

项目编号： No.81472589

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： 徐小洁

作者单位： 中国人民解放军军事科学院军事医学研究院

项目金额： 75万元

中文摘要： 恶性肿瘤细胞与正常细胞相比有着不同的糖代谢表型。研究肿瘤细胞的糖代谢机制以及发现这一过程中新的重要调控分子对于早期诊断和治疗肿瘤具有重要作用。我们的前期工作发现了一个新的促进肿瘤糖代谢并能与肿瘤糖代谢途径中的核心分子HIF1α相互作用的蛋白即HPIP。因此，我们拟利用RNA干扰、细胞免疫荧光、免疫沉淀、Western-blot等技术深入研究HPIP对HIF1α的调控机制；利用葡萄糖摄取检测、乳酸含量测定、线粒体耗氧量检测、生长曲线分析、细胞迁移侵袭实验、动物实验检测HPIP对肿瘤糖代谢功能的影响及糖代谢在调节这种生长和转移中的作用；利用临床标本检测HPIP和HIF1α在肿瘤患者中的表达，确定其临床意义，为阐明肿瘤发生发展的分子机制提供新的线索和潜在的治疗靶标。

中文关键词： HPIP；肿瘤；糖代谢；HIF-1α

英文摘要： Malignant tumor cells have different glucose metabolic phenotype compared to normal cells. Research on the mechanism of glucose metabolism in tumor cells and discovery of novel important regulatory molecules in this process plays an important role in early diagnosis and treatment of tumor. Our previous study found a novel molecule, HPIP, which could promote tumor glucose metabolism and could interact with the core molecule in tumor glucose metabolic pathways, HIF1α. Therefore, RNA interference, cell immunofluorescence, precipitation, Western blot analysis are to be performed to study regulatory mechanism of HIF1α by HPIP in-depth. Experiment such as glucose uptake detection, determination of lactic acid content, oxygen consumption of mitochondria, growth curve analysis, cell migration experiment, animal experiment are to be performed to test the effect of HPIP on tumor glucose metabolism as well as regulation of the growth and metastasis. Clinical significance of HPIP and HIF1α are to be determined in the clinical samples of tumor patients, which contributes to elucidating the molecular mechanisms of cancer development and providing new clues and potential therapeutic targets.

英文关键词： HPIP;tumor;glucose metabolism;HIF-1α