Nrf2: bane or blessing in cancer?

J Cancer Res Clin Oncol. 2014 Aug;140(8):1251-9. doi: 10.1007/s00432-014-1627-1. Epub 2014 Mar 6.

Abstract

Background: The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor-E2-related factor 2 (Nrf2)-antioxidant response element pathway serves a major function in endogenous cytoprotection in normal cells. Nrf2 is a transcription factor that mainly regulates the expression of a wide array of genes that produce the antioxidants and other proteins responsible for the detoxification of xenobiotics and reactive oxygen species. Nrf2 mediates the chemoprevention of cancer in normal cells.

Results and discussion: Growing body of evidence suggests that Nrf2 is not only involved in the chemoprevention of normal cells but also promotes the growth of cancer cells. However, the mechanism underlying the function of Nrf2 in oncogenesis and tumor protection in cancer cells remains unclear and thus requires further study.

Conclusion: This review aims to rationalize the existing functions of Nrf2 in chemoprevention and tumorigenesis, as well as the somatic mutations of Nrf2 and Keap1 in cancer and Nrf2 cross talk with miRNAs. This review also discusses the future challenges in Nrf2 research.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kelch-Like ECH-Associated Protein 1
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Mutation
  • NF-E2-Related Factor 2 / physiology*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / prevention & control
  • Reactive Oxygen Species / metabolism

Substances

  • Anticarcinogenic Agents
  • Intracellular Signaling Peptides and Proteins
  • KEAP1 protein, human
  • Kelch-Like ECH-Associated Protein 1
  • MicroRNAs
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Reactive Oxygen Species