title: Keap1-Nrf2 signalling in pancreatic cancer.
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.
authors.affiliation: MRC 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. Electronic address: alastair.hayes@ed.ac.uk.
authors.forename: Alastair J
authors.initials: AJ
authors.lastname: Hayes
authors.affiliation: School of Clinical Surgery, College of Medicine and Veterinary Medicine, University of Edinburgh, Room SU 305, Chancellor's Building, 49 Little France Crescent, Edinburgh, Scotland EH16 4SB, United Kingdom. Electronic address: christos.skouras@ed.ac.uk.
authors.forename: Christos
authors.initials: C
authors.lastname: Skouras
authors.affiliation: Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne, England NE1 4LP, United Kingdom. Electronic address: beate.haugk@nuth.nhs.uk.
authors.forename: Beate
authors.initials: B
authors.lastname: Haugk
authors.affiliation: Department of Hepato-Pancreatico-Biliary Surgery, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, High Heaton, Newcastle upon Tyne, England NE7 7DN, United Kingdom. Electronic address: richard.charnley@nuth.nhs.uk.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Charnley
mesh_terms: D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2
keywords: AKR1B10; Keap1; NQO1; Nrf2; Pancreatic cancer