Format

Send to

Choose Destination
Life Sci. 2019 Oct 30:116986. doi: 10.1016/j.lfs.2019.116986. [Epub ahead of print]

The Role of Nrf2 signaling in cancer stem cells: from stemness and self-renewal to tumorigenesis and chemoresistance.

Author information

1
Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Students Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
2
Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
3
Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
4
Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: drnsamadi@yahoo.com.

Abstract

Cancer stem cells (CSCs) are subpopulation of tumor mass with exclusive abilities in self-renewing, stemness maintaining, and differentiation into the various non-stem cancer cells to provoke tumorigenesis, metastasis dissemination, drug-resistant, and cancer recurrence. Reactive oxygen species (ROS) impair cellular function by oxidizing cell components containing proteins, lipids, and DNA. Tumor oxidant status is elevated due to high metabolic activity under influence of abnormal growth factors, cytokines and function ROS-producing enzymes, including nitric oxide synthases, cyclooxygenases, and lipoxygenases. Nuclear factor-erythroid 2-related factor 2 (NRF2) is a transcriptional master regulator element which is believed to recognize cellular oxidative stress followed by binding to promoter of cyto-protective and anti-oxidative genes to maintain cellular redox status through promoting antioxidant response participants (glutathione peroxidase, glutathione reductase, thioredoxin reductase, ferritin, NADPH: quinone oxidoreductase 1). However, Nrf2 signaling protects malignant cells from ROS damage against tumor growth and chemoresistance. In addition, Nrf2 is able to participate in differentiation of certain stem cells by modulating autophagy procedure, also NRF2 provokes DNA damage response and facilitates drug metabolism and drug resistance by controlling of downstream enzyme and transporter members. In this review, we discuss the role of NRF2 in stemness, self-renewal ability, tumorigenesis and chemoresistance of CSCs.

KEYWORDS:

NFE2L2; Nrf2 gene therapy; Senescence; mitochondria; quiescence

PMID:
31678283
DOI:
10.1016/j.lfs.2019.116986

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center