Journal article
Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation
Oncogene, v 37(7), pp 924-934
23 Oct 2017
PMID: 29059153
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation
- Creators
- Valerie L. Sodi - Drexel UniversityZachary A. Bacigalupa - Drexel UniversityChristina M. Ferrer - Drexel UniversityJoyce V. Lee - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USA Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA Department Medicine, Indiana University, Indianapolis, IN 46202, USAWiktoria A. Gocal - Drexel UniversityDimpi Mukhopadhyay - Drexel UniversityKathryn E. Wellen - Department of Cancer Biology; Abramson Family Cancer Research Institute; University of Pennsylvania Perelman School of Medicine; Philadelphia, PA USAMircea Ivan - Indiana University – Purdue University IndianapolisMauricio J. Reginato - Drexel University
- Publication Details
- Oncogene, v 37(7), pp 924-934
- Publisher
- Springer Nature
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000425281800009
- Scopus ID
- 2-s2.0-85042143641
- Other Identifier
- 991019168025804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Genetics & Heredity
- Oncology