NAC1促进肿瘤细胞糖酵解的机制及其作为肿瘤治疗新靶点的研究

项目名称： NAC1促进肿瘤细胞糖酵解的机制及其作为肿瘤治疗新靶点的研究

项目编号： No.81473240

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： 张熠

作者单位： 苏州大学

项目金额： 65万元

中文摘要： 糖酵解增强是肿瘤细胞能量代谢的显著特征之一，它广泛存在于各种肿瘤组织中，能够促进肿瘤细胞的增殖、增强侵袭性并介导耐药。伏隔核1（NAC1）是我们及合作团队研究发现的一个新促癌因子。我们前期实验发现NAC1能通过增强缺氧诱导因子-1α（HIF-1α）蛋白稳定性、进而促进乳酸生成和葡萄糖摄取而显著增强肿瘤糖酵解。但NAC1促进糖酵解内在机制和生物学意义不明。本研究拟在前期工作基础上，从NAC1物理性结合组蛋白去乙酰化酶HDAC4出发，研究NAC1通过去泛素化正性调控HDAC4蛋白表达而维持HIF-1α蛋白稳定性，并促进糖酵解的作用机制。进一步通过干预NAC1的表达评估其作为肿瘤治疗新靶点的可能性和重要意义。

中文关键词： 伏隔核1；糖酵解；肿瘤治疗；新靶点

英文摘要： Aerobic glycolysis is one of the hallmarks of cancer, which can be observed in various types of tumors. Cancer cells preferentially utilize glycolysis to support their proliferation, invasion, and promote therapeutic resistance. In our preliminary study, we found that NAC1, a new putative oncogene uncovered by us and our collaborators, plays a critical role in maintaining HIF-1α protein stability, thereby promoting lactate production and glucose uptake in cancer cells. In this proposal, we will investigate the molecular mechanism underlying how NAC1 contributes to glycolysis and its implication in cancer biology and treatment. We will investigate the molecular interaction between NAC1 and HDAC4 and determine whether NAC1 promotes glycolysis through maintaining HDAC4 stability by its deubiquitinating activity, leading to inhibition of HIF-1α acetylation and enhancement of its stability. We will further explore the potential of NAC1 as a novel target for cancer treatment.

英文关键词： NAC1;glycolysis;cancer therapy;novel target