Keap1-Nrf2 signalling in pancreatic cancer

Alastair J Hayes, Christos Skouras, Beate Haugk, Richard M Charnley

Research output: Contribution to journalLiterature reviewpeer-review

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.

Original languageEnglish
Pages (from-to)288-299
Number of pages12
JournalInternational Journal of Biochemistry and Cell Biology
Volume65
Early online date24 Jun 2015
DOIs
Publication statusPublished - Aug 2015

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