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

V. L. Sodi, Z. A. Bacigalupa, C. M. Ferrer, J. V. Lee, W. A. Gocal, D. Mukhopadhyay, K. E. Wellen, Mircea Ivan, M. J. Reginato

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)924-934
Number of pages11
JournalOncogene
Volume37
Issue number7
DOIs
StatePublished - Feb 15 2018

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Sterol Regulatory Element Binding Protein 1
Lipid Metabolism
Food
Neoplasms
Lipids
AMP-Activated Protein Kinases
O-GlcNAc transferase
Cell Survival
Carcinogenesis
Transcription Factors
Enzymes
Growth

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Sodi, 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. https://doi.org/10.1038/onc.2017.395

Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation. / Sodi, V. L.; Bacigalupa, Z. A.; Ferrer, C. M.; Lee, J. V.; Gocal, W. A.; Mukhopadhyay, D.; Wellen, K. E.; Ivan, Mircea; Reginato, M. J.

In: Oncogene, Vol. 37, No. 7, 15.02.2018, p. 924-934.

Research output: Contribution to journalArticle

Sodi, VL, Bacigalupa, ZA, Ferrer, CM, Lee, JV, Gocal, WA, Mukhopadhyay, D, Wellen, KE, Ivan, M & Reginato, MJ 2018, 'Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation', Oncogene, vol. 37, no. 7, pp. 924-934. https://doi.org/10.1038/onc.2017.395
Sodi VL, Bacigalupa ZA, Ferrer CM, Lee JV, Gocal WA, Mukhopadhyay D et al. Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation. Oncogene. 2018 Feb 15;37(7):924-934. https://doi.org/10.1038/onc.2017.395
Sodi, V. L. ; Bacigalupa, Z. A. ; Ferrer, C. M. ; Lee, J. V. ; Gocal, W. A. ; Mukhopadhyay, D. ; Wellen, K. E. ; Ivan, Mircea ; Reginato, M. J. / Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation. In: Oncogene. 2018 ; Vol. 37, No. 7. pp. 924-934.
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