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Keap1-Nrf2 signalling in pancreatic cancer
Alastair J Hayes1, Christos Skouras2, Beate Haugk3
1MRC Centre for Inflammation Research, University of Edinburgh, Queen's Medical Research Centre, Room C2.18, 47 Little France Crescent, Edinburgh, Scotland EH16 4TJ, United Kingdom.
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.
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