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The emerging role of the Nrf2–Keap1 signaling pathway in cancer

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Jaramillo, Melba C., Zhang, Donna D.·2013·Genes & Development
DOI 10.1101/gad.225680.113
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Abstract

The Nrf2 (nuclear factor erythroid 2 [NF-E2]-related factor 2 [Nrf2])–Keap1 (Kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein 1) signaling pathway is one of the most important cell defense and survival pathways. Nrf2 can protect cells and tissues from a variety of toxicants and carcinogens by increasing the expression of a number of cytoprotective genes. As a result, several Nrf2 activators are currently being tested as chemopreventive compounds in clinical trials. Just as Nrf2 protects normal cells, studies have shown that Nrf2 may also protect cancer cells from chemotherapeutic agents and facilitate cancer progression. Nrf2 is aberrantly accumulated in many types of cancer, and its expression is associated with a poor prognosis in patients. In addition, Nrf2 expression is induced during the course of drug resistance. Collectively, these studies suggest that Nrf2 contributes to both intrinsic and acquired chemoresistance. This discovery has opened up a broad spectrum of research geared toward a better understanding of the role of Nrf2 in cancer. This review provides an overview of (1) the Nrf2–Keap1 signaling pathway, (2) the dual role of Nrf2 in cancer, (3) the molecular basis of Nrf2 activation in cancer cells, and (4) the challenges in the development of Nrf2-based drugs for chemoprevention and chemotherapy.

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Metadata

Authors
Jaramillo, M. C., & Zhang, D. D.
Venue
Genes & Development
Publisher
Cold Spring Harbor Laboratory
Published
2013-10-15
Volume
27
Issue
20
Pages
2179-2191
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
DOI
10.1101/gad.225680.113
OpenAlex
W2138271341
Cited by
1,297
References
33
Type
posted content
Language
en
Open access
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Jaramillo, M. C., & Zhang, D. D. (2013). The emerging role of the Nrf2–Keap1 signaling pathway in cancer. Genes & Development. https://doi.org/10.1101/gad.225680.113

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