Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
FEBS Lett. 2022 Aug;596(16):1981-1993. doi: 10.1002/1873-3468.14458. Epub 2022 Aug 2.
Nuclear factor erythroid-derived 2-like 2 (NRF2) is a master transcription factor that coordinately regulates the expression of many cytoprotective genes and plays a central role in defense mechanisms against oxidative and electrophilic insults. Although increased NRF2 activity is principally beneficial for our health, NRF2 activation in cancer cells is detrimental. Many human cancers exhibit persistent NRF2 activation and such cancer cells rely on NRF2 for most of their malignant characteristics, such as therapeutic resistance and aggressive tumourigenesis, and thus fall into NRF2 addiction. The persistent activation of NRF2 confers great advantages on cancer cells, whereas it is not tolerated by normal cells, suggesting that certain requirements are necessary for a cell to exploit NRF2 and evolve into malignant cancer cells. In this review, recent reports and data on the genetic, metabolic and immunological features of NRF2-activated cancer cells are summarized, and prerequisites for NRF2 addiction in cancer cells and their therapeutic applications are discussed.
核因子红细胞 2 相关因子 2（NRF2）是一种主转录因子，它协调调节许多细胞保护基因的表达，在对抗氧化和亲电应激的防御机制中发挥核心作用。虽然增加 NRF2 的活性主要对我们的健康有益，但 NRF2 在癌细胞中的激活是有害的。许多人类癌症表现出持续的 NRF2 激活，并且这些癌细胞依赖于 NRF2 来获得其大部分恶性特征，例如治疗耐药性和侵袭性肿瘤发生，因此它们陷入了 NRF2 成瘾。NRF2 的持续激活赋予癌细胞巨大的优势，而正常细胞则不能耐受，这表明细胞需要某些条件才能利用 NRF2 并演变成恶性癌细胞。在这篇综述中，总结了 NRF2 激活的癌细胞的遗传、代谢和免疫学特征的最新报告和数据，并讨论了癌细胞中 NRF2 成瘾的先决条件及其治疗应用。
