PMID- 29524020 OWN - NLM STAT- MEDLINE DCOM- 20190611 LR - 20211204 IS - 1573-6881 (Electronic) IS - 0145-479X (Linking) VI - 50 IP - 3 DP - 2018 Jun TI - Cross regulation between mTOR signaling and O-GlcNAcylation. PG - 213-222 LID - 10.1007/s10863-018-9747-y [doi] AB - The hexosamine biosynthetic pathway (HBP) integrates glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis. UDP-GlcNAc is the nucleotide sugar donor for O-linked beta-N-acetylglucosaminylation (O-GlcNAcylation) processes. O-GlcNAc transferase (OGT) is the enzyme which transfers the N-acetylglucosamine (O-GlcNAc) residue onto target proteins. Several studies previously showed that glucose metabolism dysregulations associated with obesity, diabetes or cancer correlated with an increase of OGT expression and global O-GlcNAcylation levels. Moreover, these diseases present an increased activation of the nutrient sensing mammalian target of rapamycin (mTOR) pathway. Other works demonstrate that mTOR regulates protein O-GlcNAcylation in cancer cells through stabilization of OGT. In this context, we studied the cross-talk between these two metabolic sensors in vivo in obese mice predisposed to diabetes and in vitro in normal and colon cancer cells. We report that levels of OGT and O-GlcNAcylation are increased in obese mice colon tissues and colon cancer cells and are associated with a higher activation of mTOR signaling. In parallel, treatments with mTOR regulators modulate OGT and O-GlcNAcylation levels in both normal and colon cancer cells. However, deregulation of O-GlcNAcylation affects mTOR signaling activation only in cancer cells. Thus, a crosstalk exists between O-GlcNAcylation and mTOR signaling in contexts of metabolism dysregulation associated to obesity or cancer. FAU - Very, Ninon AU - Very N AD - CNRS, UMR 8576 - UGSF - Unite de Glycobiologie Structurale et Fonctionnelle, Universite de Lille, F 59000, Lille, France. FAU - Steenackers, Agata AU - Steenackers A AD - Laboratory of Cell Biochemistry and Biology, NIDDK, National Institutes of Health, Bethesda, MD, USA. FAU - Dubuquoy, Caroline AU - Dubuquoy C AD - INSERM, U995, LIRIC - Lille Inflammation Research International Center, CHU Lille, Universite de Lille, F 59000, Lille, France. FAU - Vermuse, Jeanne AU - Vermuse J AD - CNRS, UMR 8576 - UGSF - Unite de Glycobiologie Structurale et Fonctionnelle, Universite de Lille, F 59000, Lille, France. FAU - Dubuquoy, Laurent AU - Dubuquoy L AD - INSERM, U995, LIRIC - Lille Inflammation Research International Center, CHU Lille, Universite de Lille, F 59000, Lille, France. FAU - Lefebvre, Tony AU - Lefebvre T AD - CNRS, UMR 8576 - UGSF - Unite de Glycobiologie Structurale et Fonctionnelle, Universite de Lille, F 59000, Lille, France. FAU - El Yazidi-Belkoura, Ikram AU - El Yazidi-Belkoura I AD - CNRS, UMR 8576 - UGSF - Unite de Glycobiologie Structurale et Fonctionnelle, Universite de Lille, F 59000, Lille, France. ikram.el-yazidi@univ-lille1.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180309 PL - United States TA - J Bioenerg Biomembr JT - Journal of bioenergetics and biomembranes JID - 7701859 RN - EC 2.4.1.- (N-Acetylglucosaminyltransferases) RN - EC 2.4.1.- (O-GlcNAc transferase) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - V956696549 (Acetylglucosamine) SB - IM MH - Acetylglucosamine/*metabolism MH - Animals MH - Colonic Neoplasms/metabolism MH - Glycosylation MH - Mice MH - Mice, Obese MH - N-Acetylglucosaminyltransferases/metabolism MH - Obesity/metabolism MH - Receptor Cross-Talk MH - *Signal Transduction MH - TOR Serine-Threonine Kinases/*metabolism OTO - NOTNLM OT - Cancer OT - Colon OT - Metabolism OT - O-GlcNAcylation OT - Obesity OT - mTOR signaling EDAT- 2018/03/11 06:00 MHDA- 2019/06/14 06:00 CRDT- 2018/03/11 06:00 PHST- 2017/10/19 00:00 [received] PHST- 2018/02/15 00:00 [accepted] PHST- 2018/03/11 06:00 [pubmed] PHST- 2019/06/14 06:00 [medline] PHST- 2018/03/11 06:00 [entrez] AID - 10.1007/s10863-018-9747-y [pii] AID - 10.1007/s10863-018-9747-y [doi] PST - ppublish SO - J Bioenerg Biomembr. 2018 Jun;50(3):213-222. doi: 10.1007/s10863-018-9747-y. Epub 2018 Mar 9.