摘要
Physiological concentrations of reactive oxygen species (ROS) play vital roles in various normal cellular processes, whereas excessive ROS generation is central to disease pathogenesis. The nuclear factor erythroid 2-related factor 2 (NRF2) is a critical transcription factor that regulates the cellular antioxidant systems in response to oxidative stress by governing the expression of genes encoding antioxidant enzymes that shield cells from diverse oxidative alterations. NRF2 and its negative regulator Kelch-like ECH-associated protein 1 (KEAP1) have been the focus of numerous investigations in elucidating whether NRF2 suppresses tumor promotion or conversely exerts pro-oncogenic effects. NRF2 has been found to participate in various pathological processes, including dysregulated cell proliferation, metabolic remodeling, and resistance to apoptosis. Herein, this review article will examine the intriguing role of phase separation in activating the NRF2 transcriptional activity and explore the NRF2 dual impacts on tumor immunology, cancer stem cells, metastasis, and long non-coding RNAs (LncRNAs). Taken together, this review aims to discuss the NRF2 multifaceted roles in both cancer prevention and promotion while also addressing the advantages, disadvantages, and limitations associated with modulating NRF2 therapeutically in cancer treatment.
摘要译文
活性氧（ROS）的生理浓度在各种正常细胞过程中起着至关重要的作用，而过度的ROS产生对于疾病发病机理至关重要。核因子2与2相关因子2（NRF2）是一个关键转录因子，它通过控制编码抗氧化氧化细胞的抗氧化剂的基因的表达来调节细胞抗氧化剂系统对氧化应激的反应。NRF2及其阴性调节剂Kelch样ECH相关蛋白1（KEAP1）一直是众多研究的重点，以阐明NRF2抑制肿瘤促进还是相反施加亲源性作用。已经发现NRF2参与了各种病理过程，包括细胞增殖失调，代谢重塑和对凋亡的耐药性。在此，本评论文章将研究相分离在激活NRF2转录活性中的有趣作用，并探索NRF2双重影响对肿瘤免疫学，癌症干细胞，转移和长期非编码RNA（LNCRNA）的影响。综上所述，这篇综述旨在讨论NRF2在预防和促进中的多方面角色，同时还解决与在癌症治疗中调节NRF2相关的优势，缺点和局限性。
Christophe Glorieux;Cinthya Enríquez;Constanza González;Gabriela Aguirre-Martínez;Pedro Buc Calderon. The Multifaceted Roles of NRF2 in Cancer: Friend or Foe?[J]. Antioxidants, 2024,13(1): 70