دورية أكاديمية
Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation.
| العنوان: | Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation. |
|---|---|
| المؤلفون: | 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. |
| المصدر: | Oncogene [Oncogene] 2018 Feb 15; Vol. 37 (7), pp. 924-934. Date of Electronic Publication: 2017 Oct 23. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5594 (Electronic) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2002->: Basingstoke : Nature Publishing Group Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987- |
| مواضيع طبية MeSH: | Gene Expression Regulation, Neoplastic* , Lipogenesis*, Biomarkers, Tumor/*metabolism , Breast Neoplasms/*metabolism , Breast Neoplasms/*pathology , N-Acetylglucosaminyltransferases/*metabolism , Sterol Regulatory Element Binding Protein 1/*metabolism, Animals ; Apoptosis ; Biomarkers, Tumor/genetics ; Breast Neoplasms/genetics ; Cell Proliferation ; Female ; Humans ; Lipids/analysis ; Mice ; Mice, Nude ; N-Acetylglucosaminyltransferases/genetics ; Nutrients/metabolism ; Signal Transduction ; Sterol Regulatory Element Binding Protein 1/genetics ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays |
| مستخلص: | 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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| معلومات مُعتمدة: | F31 CA183574 United States CA NCI NIH HHS; F31 CA192868 United States CA NCI NIH HHS; R01 CA155413 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (Biomarkers, Tumor) 0 (Lipids) 0 (SREBF1 protein, human) 0 (Sterol Regulatory Element Binding Protein 1) EC 2.4.1.- (N-Acetylglucosaminyltransferases) EC 2.4.1.255 (OGT protein, human) |
| تواريخ الأحداث: | Date Created: 20171024 Date Completed: 20190306 Latest Revision: 20191210 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC5814337 |
| DOI: | 10.1038/onc.2017.395 |
| PMID: | 29059153 |
| قاعدة البيانات: | MEDLINE |
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