GAPDH在乳腺癌细胞EMT及乳腺癌转移中的表达与功能研究

项目名称： GAPDH在乳腺癌细胞EMT及乳腺癌转移中的表达与功能研究

项目编号： No.81472463

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： 赵倩

作者单位： 上海交通大学

项目金额： 80万元

中文摘要： 肿瘤转移是恶性肿瘤导致患者死亡的首要因素。上皮-间质转化(Epithelial-mesenchymal transition, EMT)是指上皮细胞通过特定程序转化为间质细胞的过程，是恶性肿瘤细胞获得转移能力的重要步骤。肿瘤细胞的代谢在整体上发生改变，其显著特征是肿瘤细胞在有氧状态下也优先进行糖酵解，而不是通过氧化磷酸化提供能量，即Warburg效应。我们在前期研究中发现Snail和TGF-B诱导细胞发生EMT时，参与糖酵解的3-磷酸甘油醛脱氢酶（GAPDH）蛋白水平显著升高， RNA干扰实验初步证明其参与乳腺癌细胞的转移，在此基础上，我们拟对GAPDH蛋白在EMT中上调的分子机制及其参与乳腺癌转移的途径和机制进行深入研究，结合临床乳腺癌病人GAPDH水平与肿瘤转移相关性的研究，旨在揭示EMT和肿瘤转移过程中葡萄糖代谢改变的原因和结果，为明确肿瘤EMT和转移发生的分子机理提供新的理论依据。

中文关键词： C21乳腺肿瘤；三磷酸甘油醛脱氢酶；上皮间质转化；肿瘤转移；自噬

英文摘要： Metastases are the leading factor of cancer-related mortality. Epithelial-mesenchymal transition (EMT) is a process in which adherent epithelial cells shed their epithelial traits and acquire mesenchymal properties, which is thought to be important step for the progression of tumor cells to invasive and metastatic cells. Malignant cells characteristically exhibit altered metabolic patterns when compared with normal mammalian cells with increased reliance on anaerobic metabolism of glucose to lactic acid through glycolysis even in the presence of abundant oxygen. The inefficiency of the anaerobic pathway is compensated by increased glucose flux, a phenomenon first noted by Otto Warburg called aerobic glycolysis. Our previous study shows that the protein level of Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), one of the enzymes involved in glycolysis, is upregulated during the Snail as well as TGF-beta-induced EMT process. The migration of breast cancer cells are partially blocked by knock down of GAPDH, suggesting that GAPDH may play an import role in breast cancer cell migration. We plan to investigate the molecular mechanism of the upregulation of GAPDH in the EMT of breast cancer cells. Meanwhile the mechanism through which GAPDH taking part in the migration and metastasis will also be deciphered. Moreover, through the relationship study of GAPDH expession and the metastasis status of clinical breast cancer patients, the character of Glucose metabolism in the EMT and breast cancer metastasis will be futher deciphered. The above research should shed new lights to the mechanism study of EMT and metastasis in breast cancer.

英文关键词： breast cancer;GAPDH;EMT;metastasis;autophagy