Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Emerging Role of NRF2 Signaling in Cancer Stem Cell Phenotype

  • Steffanus P. Hallis (Department of Pharmacy, Graduate School, The Catholic University of Korea) ;
  • Jin Myung Kim (Department of Pharmacy, Graduate School, The Catholic University of Korea) ;
  • Mi-Kyoung Kwak (Department of Pharmacy, Graduate School, The Catholic University of Korea)
  • Received : 2022.12.28
  • Accepted : 2023.02.09
  • Published : 2023.03.31
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Abstract

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.

Keywords

Acknowledgement

This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2022R1A2C2011866, 2018R1A6A1A03025108). This study was also supported by The Catholic University of Korea, Research Fund 2021.

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