Keap1-Nrf2 通路在癌症中的作用。
Role of the Keap1-Nrf2 pathway in cancer.
机构信息
Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, Kuopio, Finland.
Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, Kuopio, Finland; Institute of Biomedicine, School of Medicine, University of Eastern Finland, P.O. Box 1627, Kuopio, Finland.
出版信息
Adv Cancer Res. 2014;122:281-320. doi: 10.1016/B978-0-12-420117-0.00008-6.
The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) pathway is one of the major signaling cascades involved in cell defense and survival against endogenous and exogenous stress. While Nrf2 and its target genes provide protection against various age-related diseases including tumorigenesis, constitutively active Nrf2 in cancer cells increases the expression of cytoprotective genes and, consequently, enhances proliferation via metabolic reprogramming and inhibition of apoptosis. Herein, we review the current understanding of the regulation of Nrf2 in normal cells as well as its dual role in cancer. Furthermore, the mechanisms of Nrf2 dysregulation in cancer, consequences of unchecked Nrf2 activity, and therapies targeting the Keap1-Nrf2 system are discussed.
Kelch 样 ECH 相关蛋白 1（Keap1）-核因子 E2 相关因子 2（Nrf2）通路是参与细胞防御和生存以对抗内源性和外源性应激的主要信号级联反应之一。虽然 Nrf2 及其靶基因提供了对各种与年龄相关的疾病（包括肿瘤发生）的保护，但癌细胞中持续激活的 Nrf2 会增加细胞保护基因的表达，从而通过代谢重编程和抑制细胞凋亡来促进增殖。本文综述了 Nrf2 在正常细胞中的调节作用及其在癌症中的双重作用。此外，还讨论了癌症中 Nrf2 失调的机制、不受控制的 Nrf2 活性的后果以及针对 Keap1-Nrf2 系统的治疗方法。
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