Dysregulation of the Keap1-Nrf2 pathway in cancer

Biochem Soc Trans. 2015 Aug;43(4):645-9. doi: 10.1042/BST20150048. Epub 2015 Aug 3.

Abstract

Accumulating evidence suggests that dysregulation of the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) pathway resulting in constitutively active Nrf2 and increased expression of cytoprotective Nrf2 target genes, has a pivotal role in cancer. Cancer cells are able to hijack the Keap1-Nrf2 system via multiple mechanisms leading to enhanced chemo- and radio-resistance and proliferation via metabolic reprogramming as well as inhibition of apoptosis. In this mini-review, we will describe the mechanisms leading to increased Nrf2 activity in cancer with a focus on the information achieved from large-scale multi-omics projects across various cancer types.

Keywords: Kelch-like ECH-associated protein 1 (Keap1); The Cancer Genome Atlas (TCGA); cancer; genome; nuclear factor E2-related factor 2 (Nrf2); oxidative stress.

Publication types

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

MeSH terms

  • Apoptosis
  • Cell Proliferation
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Gene Expression Regulation, Neoplastic* / radiation effects
  • Genomics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2 / genetics*
  • Neoplasms / genetics*
  • Radiation Tolerance

Substances

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