The Hexosamine Biosynthesis Pathway Is Essential for Pancreatic Beta Cell Development* TheHexosamineBiosynthesisPathwayIsEssentialfor PancreaticBetaCellDevelopment* Receivedforpublication,May26,2009 Published,JBCPapersinPress,July7,2009,DOI10.1074/jbc.M109.025288 Gae¨lleFilhoulaud1,GhislaineGuillemain2,andRaphae¨lScharfmann filexlib. The hexosamine biosynthetic pathway and O-GlcNAcylation drive the expression of -catenin and cell proliferation Stéphanie Olivier-Van Stichelen,1 Céline Guinez,1 Anne-Marie Mir,1 Yobana Perez-Cervera,1 Chunming Liu,2 Jean-Claude Michalski,1 and Tony Lefebvre1 1CNRS-UMR 8576, Unit of Structural and Functional Glycobiology, University of Lille 1, Villeneuve d'Ascq, France; and Abstract: Alterations in glucose and glutamine utilizing pathways and in fatty acid metabolism are currently considered the most significant and prevalent metabolic changes observed in almost all types of tumors. Glucose, glutamine and fatty acids are the substrates for the hexosamine biosynthetic pathway (HBP). The hexosamine biosyn- thetic pathway utilizes up to 2-5% of glucose that enters a non-cancer cell and along with glutamine, acetyl- coenzyme A (Ac-CoA) and uridine-5′-triphosphate (UTP) are used to produce the amino sugar UDP-GlcNAc [ 5]. The HBP and glycolysis share the first two steps and di- verge at fructose-6-phosphate (F6P) (Fig. 1).
The hexosamine biosynthetic pathway. Glucose enters the cell and undergoes two-step conversion to fructose-6P (fructose-6-phosphate), after which approximately 95% of it proceeds to glycolysis and 3-5% of it is converted to glucosamine-6P (glucosamine-6-phosphate) by the enzyme GFAT (glutamine:fructose-6-phosphate amidotransferase), utilizing glutamine that enters the cell.
The epithelial-mesenchymal transition (EMT) is a highly conserved program necessary for orchestrating distant cell migration during embryonic development. Multiple studies in cancer have demonstrated a critical role for EMT during the initial stages of tumorigenesis and later during tumor invasion. Transcription factors (TFs) such as SNAIL, TWIST, and ZEB are master EMT regulators that are
Kolm-Litty V, Sauer U, Nerlich A, Lehmann F, Schleicher ED. High glucose-induced transforming growth factor β1 production is mediated by the hexosamine pathway in porcine glomerular mesangial cells. J Clin Invest 1998;101:160-169. PubMed CAS Google Scholar. McClain DA, Paterson AJ, Roos MD, Wei X, Kudlow JE.
In this study, we demonstrated an essential function of the hexosamine biosynthesis pathway (HBP)-associated O -linked β- N -acetylglucosamine ( O -GlcNAc) signaling in influenza A virus (IAV)-induced cytokine storm. O -GlcNAc transferase (OGT), a key enzyme for protein O -GlcNAcylation, mediated IAV-induced cytokine production.
ObjectivesOsteosarcoma is a malignant bone tumor with poor outcomes affecting the adolescents and elderly. In this study, we comprehensively assessed the metabolic characteristics of osteosarcoma patients and constructed a hexosamine biosynthesis pathway (HBP)-based risk score model to predict the prognosis and tumor immune infiltration in patients with osteosarcoma.MethodsGene expression
The glucose-requiring hexosamine biosynthetic pathway (HBP), which produces UDP-N-acetylglucosamine for glycosylation reactions, promotes lung adenocarcinoma (LUAD) progression. However, lung tumor cells often reside in low-nutrient microenvironments, and whether the HBP is involved in the adaptation of LUAD to nutrient stress is unknown. Here, we show that the HBP and the coat complex II