Role of the Keap1-Nrf2 pathway in cancer

Adv Cancer Res. 2014;122:281-320. doi: 10.1016/B978-0-12-420117-0.00008-6.

Abstract

The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) pathway is one of the major signaling cascades involved in cell defense and survival against endogenous and exogenous stress. While Nrf2 and its target genes provide protection against various age-related diseases including tumorigenesis, constitutively active Nrf2 in cancer cells increases the expression of cytoprotective genes and, consequently, enhances proliferation via metabolic reprogramming and inhibition of apoptosis. Herein, we review the current understanding of the regulation of Nrf2 in normal cells as well as its dual role in cancer. Furthermore, the mechanisms of Nrf2 dysregulation in cancer, consequences of unchecked Nrf2 activity, and therapies targeting the Keap1-Nrf2 system are discussed.

Keywords: Antioxidants; Cancer; Chemoresistance; Keap1; Metabolic reprogramming; Nrf2; Oxidative stress; Radioresistance.

Publication types

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

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Apoptosis
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2 / metabolism*
  • Neoplasms / metabolism*
  • Neoplasms / therapy
  • Oxidative Stress
  • Prognosis
  • Signal Transduction

Substances

  • Antioxidants
  • Intracellular Signaling Peptides and Proteins
  • KEAP1 protein, human
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human