Keap1–Nrf2 signalling in pancreatic cancer. (August 2015)

• Record Type: Journal Article
• Authors: Hayes, Alastair J.; Skouras, Christos; Haugk, Beate; Charnley, Richard M.
• Is Part Of: International journal of biochemistry & cell biology. Volume 65(2015:Aug.)
• Page Start: 288
• Page End: 299
• Publication Date: 2015-08
• Subjects: AKR1B10 Aldo–keto reductase family 1 b10 -- ARE antioxidant response element -- Bach1 BTB and CNC homology 1 -- CNC Cap 'n' collar -- Cul3 Cullin-3 -- ER endoplasmic reticulum -- GCLC glutamate–cysteine ligase catalytic -- HO-1 heme oxygenase 1 -- Keap1 Kelch-like ECH-associated protein 1 -- MRPs multi-drug resistance associated protein transporters -- Nfe2l2 nuclear factor (erythroid-derived 2)-like 2 -- NFκB nuclear factor kappa-light-chain-enhancer of activated B cells -- NQO1 NAD(P)H:quinone oxidoreductase 1 -- Nrf2 nuclear factor E2 p45-related factor 2 -- PDAC pancreatic ductal adenocarcinoma -- PERK PKR-like ER kinase -- ROS reactive oxygen species -- STAT3 signal transducer and activator of transcription 3 -- TP53INP1 tumor protein p53-induced nuclear protein 1; Nrf2 -- Keap1 -- NQO1 -- AKR1B10 -- Pancreatic cancer; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2015.06.017
• Languages: English
• ISSNs: 1357-2725

Abstract

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.