» Articles » PMID: 34202320

Nrf2 in Cancer, Detoxifying Enzymes and Cell Death Programs

Overview
Date 2021 Jul 2
PMID 34202320
Citations 19
Authors
Affiliations
Soon will be listed here.
Abstract

Reactive oxygen species (ROS) play an important role in cell proliferation and differentiation. They are also by-products of aerobic living conditions. Their inherent reactivity poses a threat for all cellular components. Cells have, therefore, evolved complex pathways to sense and maintain the redox balance. Among them, Nrf2 (Nuclear factor erythroid 2-related factor 2) plays a crucial role: it is activated under oxidative conditions and is responsible for the expression of the detoxification machinery and antiapoptotic factors. It is, however, a double edge sword: whilst it prevents tumorigenesis in healthy cells, its constitutive activation in cancer promotes tumour growth and metastasis. In addition, recent data have highlighted the importance of Nrf2 in evading programmed cell death. In this review, we will focus on the activation of the Nrf2 pathway in the cytoplasm, the molecular basis underlying Nrf2 binding to the DNA, and the dysregulation of this pathway in cancer, before discussing how Nrf2 contributes to the prevention of apoptosis and ferroptosis in cancer and how it is likely to be linked to detoxifying enzymes containing selenium.

Citing Articles

Low miR-936-mediated upregulation of Pim-3 drives sorafenib resistance in liver cancer through ferroptosis inhibition by activating the ANKRD18A/Src/NRF2 pathway.

Li X, Cui M, Xu L, Guo Q Front Oncol. 2024; 14:1483660.

PMID: 39507762 PMC: 11540556. DOI: 10.3389/fonc.2024.1483660.


Medicinal plants as a potential resource for the discovery of novel structures towards cancer drug resistance treatment.

Nguyen M, Nguyen T, Le T, Le T, Chau N, Le T Heliyon. 2024; 10(20):e39229.

PMID: 39492898 PMC: 11530815. DOI: 10.1016/j.heliyon.2024.e39229.


Potential pathogenic roles of ferroptosis and cuproptosis in cadmium-induced or exacerbated cardiovascular complications in individuals with diabetes.

Saedi S, Tan Y, Watson S, Wintergerst K, Cai L Front Endocrinol (Lausanne). 2024; 15:1461171.

PMID: 39415790 PMC: 11479913. DOI: 10.3389/fendo.2024.1461171.


The activation of LBH-CRYAB signaling promotes cardiac protection against I/R injury by inhibiting apoptosis and ferroptosis.

Wu A, Zhong C, Song X, Yuan W, Tang M, Shu T iScience. 2024; 27(5):109510.

PMID: 38660406 PMC: 11039335. DOI: 10.1016/j.isci.2024.109510.


Activation of Heme Oxygenase-1 by Mangiferin in Human Retinal Pigment Epithelial Cells Contributes to Blocking Oxidative Damage.

Park C, Cha H, Hwangbo H, Bang E, Kim H, Yun S Biomol Ther (Seoul). 2024; 32(3):329-340.

PMID: 38586992 PMC: 11063488. DOI: 10.4062/biomolther.2023.175.


References
1.
Malhotra D, Portales-Casamar E, Singh A, Srivastava S, Arenillas D, Happel C . Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis. Nucleic Acids Res. 2010; 38(17):5718-34. PMC: 2943601. DOI: 10.1093/nar/gkq212. View

2.
Stafford W, Peng X, Olofsson M, Zhang X, Luci D, Lu L . Irreversible inhibition of cytosolic thioredoxin reductase 1 as a mechanistic basis for anticancer therapy. Sci Transl Med. 2018; 10(428). PMC: 7059553. DOI: 10.1126/scitranslmed.aaf7444. View

3.
Papp L, Lu J, Bolderson E, Boucher D, Singh R, Holmgren A . SECIS-binding protein 2 promotes cell survival by protecting against oxidative stress. Antioxid Redox Signal. 2009; 12(7):797-808. PMC: 11823725. DOI: 10.1089/ars.2009.2913. View

4.
Niture S, Jaiswal A . Nrf2 protein up-regulates antiapoptotic protein Bcl-2 and prevents cellular apoptosis. J Biol Chem. 2012; 287(13):9873-9886. PMC: 3323009. DOI: 10.1074/jbc.M111.312694. View

5.
Gouge J, Satia K, Guthertz N, Widya M, Thompson A, Cousin P . Redox Signaling by the RNA Polymerase III TFIIB-Related Factor Brf2. Cell. 2015; 163(6):1375-87. PMC: 4671959. DOI: 10.1016/j.cell.2015.11.005. View