title: O-GlcNAc in cancer biology.
abstract: O-linked β-N-actylglucosamine (O-GlcNAc) is a carbohydrate post-translational modification on hydroxyl groups of serine and/or threonine residues of cytosolic and nuclear proteins. Analogous to phosphorylation, O-GlcNAcylation plays crucial regulatory roles in a variety of cellular processes. O-GlcNAc was termed a nutritional sensor, as global levels of the modification are elevated in response to increased glucose and glutamine flux into the hexosamine biosynthetic pathway. A unique feature of cancer cell energy metabolism is a shift from oxidative phosphorylation to the less efficient glycolytic pathway (Warburg effect), necessitating greatly increased glucose uptake. Additionally, to help meet increased biosynthetic demands, cancer cells also up-regulate glutamine uptake. This led us to hypothesize that the universal feature of increased glucose and glutamine uptake by cancer cells might be linked to increased O-GlcNAc levels. Indeed, recent work in many different cancer types now indicates that hyper-O-GlcNAcylation is a general feature of cancer and contributes to transformed phenotypes. In this review, we describe known/potential links between hyper-O-GlcNAcylation and specific hallmarks of cancer, including cancer cell proliferation, survival, cell stresses, invasion and metastasis, aneuploidy, and energy metabolism. We also discuss inhibition of hyper-O-GlcNAcylation as a potential novel therapeutic target for cancer treatment.
authors.affiliation: Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, 245 N 15th St. New College Building Room 10112, Philadelphia, PA, 19102, USA.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Ma
authors.forename: Keith
authors.initials: K
authors.lastname: Vosseller
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy
chemical_list: D000117:Acetylglucosamine