Hyaluronan synthases posttranslational regulation in cancer.
Hyaluronan (HA) is a critical component of cancer microenvironment that is known to increase tumor progression and aggressiveness. The synthesis of HA starts from the cytosolic precursors UDP-N-acetylglucosamine and UDP-glucuronic acid. These two sugar nucleotides have several functions in addition to glycoconjugate synthesis and glucuronidation reactions, each of which can have a critical role in cancer. HA is synthesized by a family of three HA synthase (HAS) enzymes and, in this review, we described the main posttranslational modifications that are known to regulate HA metabolism. In particular, as the main HAS in adult tissues is HAS2, we focused on the role of AMPK-mediated phosphorylation and glycosylation by O-linked N-acetylglucosamine (O-GlcNAcylation) of HAS2 which mediate HAS2 inactivation and activation, respectively. HA catabolism, furnishing glucuronic acid and N-acetylglucosamine, can represent for a cancer cell a valid source of substrates to sustain complex tumor metabolism, and we highlight a presumable metabolic fate of such sugars in tumor cells.
['Vigetti|Davide|D|', 'Passi|Alberto|A|']
D015971:Gene Expression Regulation, Enzymologic D015972:Gene Expression Regulation, Neoplastic D014453:Glucuronosyltransferase D006031:Glycosylation D006801:Humans D018960:Hyaluronan Receptors D000076002:Hyaluronan Synthases D006820:Hyaluronic Acid D007249:Inflammation D009369:Neoplasms D010766:Phosphorylation D011499:Protein Processing, Post-Translational D015398:Signal Transduction D014533:Uridine Diphosphate Glucose Dehydrogenase
O-GlcNAcylation Tumor metabolism AMPK Extracellular matrix Glycobiology Glycosaminoglycans Hyaluronic acid Proteoglycans Tumor microenvironment UDP-glucose dehydrogenase