title: Keap1/Nrf2 pathway in the frontiers of cancer and non-cancer cell metabolism.
abstract: Cancer cells adapt their metabolism to their increased needs for energy and substrates for protein, lipid and nucleic acid synthesis. Nuclear erythroid factor 2-like 2 (Nrf2) pathway is usually activated in cancers and has been suggested to promote cancer cell survival mainly by inducing a large battery of cytoprotective genes. This mini review focuses on metabolic pathways, beyond cytoprotection, which can be directly or indirectly regulated by Nrf2 in cancer cells to affect their survival. The pentose phosphate pathway (PPP) is enhanced by Nrf2 in cancers and aids their growth. PPP has also been found to be up-regulated in non-cancer tissues and other pathways, such as de novo lipogenesis, have been found to be repressed after activation of the Nrf2 pathway. The importance of these Nrf2-regulated metabolic pathways in cancer compared with non-cancer state remains to be determined. Last but not least, the importance of context about Nrf2 and cancer is highlighted as the Nrf2 pathway may be activated in cancers but its pharmacological activators are useful in chemoprevention.
authors.affiliation: Department of Pharmacology & Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A. dic16@pitt.edu.
authors.forename: Dionysios V
authors.initials: DV
authors.lastname: Chartoumpekis
authors.affiliation: Department of Pharmacology & Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.
authors.forename: Nobunao
authors.initials: N
authors.lastname: Wakabayashi
authors.affiliation: Department of Pharmacology & Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, U.S.A.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Kensler
mesh_terms: D049109:Cell Proliferation; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; 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*; D009369:Neoplasms / Q000378:metabolism*; D010427:Pentose Phosphate Pathway; 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; C495635:NFE2L2 protein, human
keywords: Kelch-like ECH-associated protein 1 (Keap1); cancer; lipogenesis; metabolism; nuclear erythroid factor 2-like 2 (Nrf2); pentose phosphate pathway