Keap1-Nrf2 signalling in pancreatic cancer

Int J Biochem Cell Biol. 2015 Aug:65:288-99. doi: 10.1016/j.biocel.2015.06.017. Epub 2015 Jun 24.

Abstract

Transcription factor NF-E2 p45-related factor 2 (Nrf2, also called Nfe2l2), a master regulator of redox homeostasis, and its dominant negative regulator, Kelch-like ECH-associated protein 1 (Keap1), together tightly control the expression of numerous detoxifying and antioxidant genes. Nrf2 and the 'antioxidant response element' (ARE)-driven genes it controls are frequently upregulated in pancreatic cancer and correlate with poor survival. Upregulation of Nrf2 is, at least in part, K-Ras oncogene-driven and contributes to pancreatic cancer proliferation and chemoresistance. In this review, we aim to provide an overview of Keap1-Nrf2 signalling as it relates to pancreatic cancer, discussing the effects of inhibiting Nrf2 or Nrf2/ARE effector proteins to increase chemosensitivity.

Keywords: AKR1B10; Keap1; NQO1; Nrf2; Pancreatic cancer.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2 / metabolism*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Signal Transduction

Substances

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