The Keap1-Nrf2 Pathway: Mechanisms of Activation and Dysregulation in Cancer

Redox Biol. 2013 Jan 18;1(1):45-9. doi: 10.1016/j.redox.2012.10.001.

Abstract

The Keap1-Nrf2 pathway is the major regulator of cytoprotective responses to oxidative and electrophilic stress. Although cell signaling pathways triggered by the transcription factor Nrf2 prevent cancer initiation and progression in normal and premalignant tissues, in fully malignant cells Nrf2 activity provides growth advantage by increasing cancer chemoresistance and enhancing tumor cell growth. In this graphical review, we provide an overview of the Keap1-Nrf2 pathway and its dysregulation in cancer cells. We also briefly summarize the consequences of constitutive Nrf2 activation in cancer cells and how this can be exploited in cancer gene therapy.

Keywords: Antioxidant response element; Cancer; Gene therapy; Keap1; Nrf2.

Publication types

  • Review

MeSH terms

  • Animals
  • Cytoskeletal Proteins / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • NF-E2-Related Factor 2 / metabolism*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / therapy

Substances

  • Cytoskeletal Proteins
  • Intracellular Signaling Peptides and Proteins
  • NF-E2-Related Factor 2