Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation.

Autor: Sodi VL; Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA., Bacigalupa ZA; Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA., Ferrer CM; Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA., Lee JV; Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Gocal WA; Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA., Mukhopadhyay D; Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA., Wellen KE; Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Ivan M; Department Medicine, Indiana University, Indianapolis, IN, USA., Reginato MJ; Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2018 Feb 15; Vol. 37 (7), pp. 924-934. Date of Electronic Publication: 2017 Oct 23.
DOI: 10.1038/onc.2017.395
Abstrakt: Elevated O-GlcNAcylation is associated with disease states such as diabetes and cancer. O-GlcNAc transferase (OGT) is elevated in multiple cancers and inhibition of this enzyme genetically or pharmacologically inhibits oncogenesis. Here we show that O-GlcNAcylation modulates lipid metabolism in cancer cells. OGT regulates expression of the master lipid regulator the transcription factor sterol regulatory element binding protein 1 (SREBP-1) and its transcriptional targets both in cancer and lipogenic tissue. OGT regulates SREBP-1 protein expression via AMP-activated protein kinase (AMPK). SREBP-1 is critical for OGT-mediated regulation of cell survival and of lipid synthesis, as overexpression of SREBP-1 rescues lipogenic defects associated with OGT suppression, and tumor growth in vitro and in vivo. These results unravel a previously unidentified link between O-GlcNAcylation, lipid metabolism and the regulation of SREBP-1 in cancer and suggests a crucial role for O-GlcNAc signaling in transducing nutritional state to regulate lipid metabolism.
Databáze: MEDLINE
Externí odkaz: