乙酰辅酶A羧化酶ACC同工酶类型转换调控机制及其在肝癌进展中的作用研究

Alteration of lipid metabolism has been increasingly recognized as a hallmark of cancer cells. Its underlying mechanisms and roles in tumor progression have been paid much attention in recent years. Acetyl Coenzyme A Carboxylase (ACC) is a rate-limiting enzyme in fatty acids synthesis, which includes two isoenzymes, ACC1 and ACC2. Our previous studies have found an unregulated ACC1 expression level and a downregulated ACC2 level in hepatocellular carcinoma cell lines and patient tissues. Considering the important regulator role of isoform shift in cell metabolism and cancer progression, it’s reasonable for us to assume that isoform shift of ACC plays a role in the hepatocellular carcinoma development, which has not been reported. In this study, we will analysis the mechanisms of ACC isoenzymes shift and its role in lipd metabolism and tumor progression using in vitro and in vivo models. It will not only enrich our knowledge for understanding the common mechanisms that underlie the processes of cancer, but also provide both experimental and theoretical support for finding new drug targets for cancer therapy.

脂肪酸代谢在肿瘤中发生了异常改变，其发生机制和在肿瘤进展中的作用是近年来肿瘤研究的热点。乙酰辅酶A羧化酶（ACC）是调控脂肪酸合成的重要限速酶，具有两种同工酶，即ACC1与ACC2。研究证实，同工酶类型转换是肿瘤细胞代谢调控的重要方式，参与肿瘤的发生与进展。然而，在肝癌中尚无ACC同工酶类型转换的相关报道。我们前期发现，肝癌细胞中ACC1表达显著升高，而ACC2则显著降低，提示肝癌细胞可能发生了由ACC2到ACC1的同工酶类型转换，其发生机制及在肝癌细胞脂代谢调控和肝癌发生与进展中的作用尚不清楚。本项目旨在利用体外细胞和体内动物模型，结合肝癌患者临床标本，初步分析肝癌细胞中ACC发生同工酶类型转换的分子机制，并深入探讨其在肝癌脂代谢调控及肝癌发生与进展中的作用。本项目的开展可进一步加深对肝癌分子病理机制的理解，同时为肿瘤治疗提供新的潜在靶点提供实验依据和理论支持。