核转录因子相关因子2的活化在肿瘤代谢中的作用  

The Role of Nrf2 Activation in Tumor Metabolism

作　　者：郭浩琰 蔡蓉 邢嵘[2] GUO Hao-Yan;CAI Rong;XING Rong(Department of Biochemistry ＆ Molecular Cell Biology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China;Department of Pathology ＆ Pathophysiology, Dalian Medical University, Dalian 116044, Liaoning, China)

机构地区：[1]上海交通大学医学院生物化学与分子细胞生物学系,上海200025 [2]大连医科大学病理学与病理生理学系,辽宁大连116044

出　　处：《中国生物化学与分子生物学报》2018年第6期581-581,582-587,共7页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No.81572691);973子课题(No.2015CB910400)资助~~

摘　　要：核转录因子(NF-E2)相关因子2(nuclear factor erythroid 2 related factor 2,Nrf2)是细胞应对外界应激的主要调控因子,通过调控多种靶基因的表达,在生理条件下减轻氧化应激,维持细胞稳态。其上游受多种因素调控,包括氧化与亲电应激、外界营养状态、细胞内代谢中间产物和能量状态等。在肿瘤细胞中,异常活跃的Nrf2使其抗氧化能力增强,并且通过介导代谢重编程(metabolic reprogramming),促进肿瘤细胞增殖和生长。Keap1(Kelch-like ECH-associated protein 1)是氧化和亲电应激感受器,通过募集泛素降解系统,对Nrf2的活性起主要调控作用。本文介绍Keap1依赖与非依赖条件下Nrf2的活化途径,着重介绍在肿瘤中Nrf2的异常活化,以及如何调控代谢重编程进而调节肿瘤细胞的合成代谢,最终促进肿瘤的进展。Nuclear factor erythroid 2（ NF-E2-related factor 2,Nrf2） is a master regulator of cellular responses against environmental or intracellular stresses,by regulating the expression of its target genes to mitigate oxidative stress under physiological conditions. Nrf2 is regulated by a variety of upstream factors including oxidative and electrophilic stresses,environmental nutrition status,metabolic intermediates and energy status in the cells,etc. Aberrant Nrf2 activation results in enhanced antioxidant capacities in cancer cells. Most importantly,Nrf2 promotes tumor cell proliferation and growth by reprogramming metabolism. The activity of Nrf2 is mainly regulated by Keap1,which acts as a sensor for oxidative and electrophilic stresses. In the present review,we mainly introduce the activation of Nrf2 in Keap1-dependent or-independent ways. We also emphasize aberrant activation of Nrf2 in the regulation of metabolic reprogramming in cancer,which in turn regulates the anabolism of tumor cells.

关 键 词：核转录因子(NF-E2)相关因子2(Nrf2) Kelch样环氧氯丙烷相关蛋白-1(Keap1) 肿瘤代谢 肿瘤增殖 

分 类 号：R730.231[医药卫生—肿瘤]