دورية أكاديمية
O-GlcNAcylation regulates breast cancer metastasis via SIRT1 modulation of FOXM1 pathway.
| العنوان: | O-GlcNAcylation regulates breast cancer metastasis via SIRT1 modulation of FOXM1 pathway. |
|---|---|
| المؤلفون: | Ferrer CM; Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA., Lu TY; 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., Katsetos CD; Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia, PA, USA.; Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, PA, USA., Sinclair DA; Paul F. Glenn Labs for the Biological Mechanisms of Aging, Department of Genetics, Harvard Medical School, Boston, MA, USA., Reginato MJ; Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA. |
| المصدر: | Oncogene [Oncogene] 2017 Jan 26; Vol. 36 (4), pp. 559-569. Date of Electronic Publication: 2016 Jun 27. |
| 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: | Breast Neoplasms/*metabolism , Forkhead Box Protein M1/*metabolism , N-Acetylglucosaminyltransferases/*metabolism , Sirtuin 1/*metabolism, Animals ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Proliferation/physiology ; Female ; Forkhead Box Protein M1/genetics ; Glycosylation ; Heterografts ; Humans ; MCF-7 Cells ; Mice ; Mice, Inbred NOD ; Neoplasm Metastasis ; Sirtuin 1/genetics |
| مستخلص: | Tumors utilize aerobic glycolysis to support growth and invasion. However, the molecular mechanisms that link metabolism with invasion are not well understood. The nutrient sensor O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) modifies intracellular proteins with N-acetylglucosamine. Cancers display elevated O-GlcNAcylation and suppression of O-GlcNAcylation inhibits cancer invasion and metastasis. Here, we show that the regulation of cancer invasion by OGT is dependent on the NAD + -dependent deacetylase SIRT1. Reducing O-GlcNAcylation elevates SIRT1 levels and activity in an AMPK (AMP-activated protein kinase α)-dependent manner. Reduced O-GlcNAcylation in cancer cells leads to SIRT1-mediated proteasomal degradation of oncogenic transcription factor FOXM1 in an MEK/ERK-dependent manner. SIRT1 is critical for OGT-mediated regulation of FOXM1 ubiquitination and reducing SIRT1 activity reverses OGT-mediated regulation of FOXM1. Moreover, we show that SIRT1 levels are required for OGT-mediated regulation of invasion and metastasis in breast cancer cells. Thus, O-GlcNAcylation is a central component linking metabolism to invasion and metastasis via an SIRT1/ERK/FOXM1 axis. Competing Interests: D.A.S. is a consultant to GlaxoSmithKline, Segterra, Ovascience, and MetroBiotech. The authors declare no conflict of interest. |
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| معلومات مُعتمدة: | F31 CA183574 United States CA NCI NIH HHS; R01 AG028730 United States AG NIA NIH HHS; R01 CA155413 United States CA NCI NIH HHS; R37 AG028730 United States AG NIA NIH HHS |
| المشرفين على المادة: | 0 (FOXM1 protein, human) 0 (Forkhead Box Protein M1) EC 2.4.1.- (N-Acetylglucosaminyltransferases) EC 2.4.1.- (O-GlcNAc transferase) EC 3.5.1.- (SIRT1 protein, human) EC 3.5.1.- (Sirtuin 1) |
| تواريخ الأحداث: | Date Created: 20160628 Date Completed: 20170926 Latest Revision: 20181113 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC5192006 |
| DOI: | 10.1038/onc.2016.228 |
| PMID: | 27345396 |
| قاعدة البيانات: | MEDLINE |
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