Department of Pharmacy, Graduate School, The Catholic University of Korea, Bucheon 14662, Korea.
College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Korea.
Mol Cells. 2023 Mar 31;46(3):153-164. doi: 10.14348/molcells.2023.2196. Epub 2023 Mar 27.
Cancer stem cells (CSCs) are a small population of tumor cells characterized by self-renewal and differentiation capacity. CSCs are currently postulated as the driving force that induces intra-tumor heterogeneity leading to tumor initiation, metastasis, and eventually tumor relapse. Notably, CSCs are inherently resistant to environmental stress, chemotherapy, and radiotherapy due to high levels of antioxidant systems and drug efflux transporters. In this context, a therapeutic strategy targeting the CSC-specific pathway holds a promising cure for cancer. NRF2 (nuclear factor erythroid 2-like 2; NFE2L2) is a master transcription factor that regulates an array of genes involved in the detoxification of reactive oxygen species/electrophiles. Accumulating evidence suggests that persistent NRF2 activation, observed in multiple types of cancer, supports tumor growth, aggressive malignancy, and therapy resistance. Herein, we describe the core properties of CSCs, focusing on treatment resistance, and review the evidence that demonstrates the roles of NRF2 signaling in conferring unique properties of CSCs and the associated signaling pathways.
癌症干细胞（CSCs）是一小部分肿瘤细胞，其特征是自我更新和分化能力。CSCs 目前被认为是诱导肿瘤起始、转移和最终肿瘤复发的内在异质性的驱动力。值得注意的是，由于高水平的抗氧化系统和药物外排转运体，CSCs 天生对环境应激、化疗和放疗具有抗性。在这种情况下，针对 CSC 特异性途径的治疗策略为癌症的治愈提供了一个有希望的方法。NRF2（核因子红细胞 2 样 2；NFE2L2）是一种主转录因子，调节涉及解毒活性氧/亲电子物质的一系列基因。越来越多的证据表明，在多种类型的癌症中观察到的持续 NRF2 激活支持肿瘤生长、侵袭性恶性肿瘤和治疗耐药性。本文描述了 CSCs 的核心特性，重点是治疗耐药性，并综述了 NRF2 信号在赋予 CSCs 独特特性和相关信号通路方面的作用的证据。
