Sodi, Valerie L.Bacigalupa, Zachary A.Ferrer, Christina M.Lee, Joyce V.Gocal, Wiktoria A.Mukhopadhyay, DimpiWellen, Kathryn E.Ivan, MirceaReginato, Mauricio J.2018-08-022018-08-022018-02-15Sodi, V. L., Bacigalupa, Z. A., Ferrer, C. M., Lee, J. V., Gocal, W. A., Mukhopadhyay, D., … Reginato, M. J. (2018). Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation. Oncogene, 37(7), 924–934. http://doi.org/10.1038/onc.2017.395https://hdl.handle.net/1805/16957Elevated 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.en-USPublisher PolicyO-GlcNAcOGTCancerLipid metabolismSREBP-1FASACLYLipogenesisArticle