| The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. | |
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MedLine Citation:
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PMID: 23217706 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Reprogramming of cellular metabolism is a key event during tumorigenesis. Despite being known for decades (Warburg effect), the molecular mechanisms regulating this switch remained unexplored. Here, we identify SIRT6 as a tumor suppressor that regulates aerobic glycolysis in cancer cells. Importantly, loss of SIRT6 leads to tumor formation without activation of known oncogenes, whereas transformed SIRT6-deficient cells display increased glycolysis and tumor growth, suggesting that SIRT6 plays a role in both establishment and maintenance of cancer. By using a conditional SIRT6 allele, we show that SIRT6 deletion in vivo increases the number, size, and aggressiveness of tumors. SIRT6 also functions as a regulator of ribosome metabolism by corepressing MYC transcriptional activity. Lastly, Sirt6 is selectively downregulated in several human cancers, and expression levels of SIRT6 predict prognosis and tumor-free survival rates, highlighting SIRT6 as a critical modulator of cancer metabolism. Our studies reveal SIRT6 to be a potent tumor suppressor acting to suppress cancer metabolism. |
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Authors:
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Carlos Sebastián; Bernadette M M Zwaans; Dafne M Silberman; Melissa Gymrek; Alon Goren; Lei Zhong; Oren Ram; Jessica Truelove; Alexander R Guimaraes; Debra Toiber; Claudia Cosentino; Joel K Greenson; Alasdair I MacDonald; Liane McGlynn; Fraser Maxwell; Joanne Edwards; Sofia Giacosa; Ernesto Guccione; Ralph Weissleder; Bradley E Bernstein; Aviv Regev; Paul G Shiels; David B Lombard; Raul Mostoslavsky |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Cell Volume: 151 ISSN: 1097-4172 ISO Abbreviation: Cell Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-10 Completed Date: 2013-02-06 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0413066 Medline TA: Cell Country: United States |
Other Details:
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Languages: eng Pagination: 1185-99 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Proliferation Down-Regulation Fibroblasts / metabolism Gene Knockout Techniques Glycolysis Humans Mice Mice, Nude Mice, SCID Neoplasm Transplantation Neoplasms / metabolism* Proto-Oncogene Proteins c-myc / metabolism Sirtuins / genetics, metabolism* Transcription, Genetic Transplantation, Heterologous Tumor Suppressor Proteins / genetics |
| Grant Support | |
ID/Acronym/Agency:
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DK088190-01A1/DK/NIDDK NIH HHS; GM093072-01/GM/NIGMS NIH HHS; GM101171/GM/NIGMS NIH HHS; K08 EB012859/EB/NIBIB NIH HHS; P50HG006193/HG/NHGRI NIH HHS; R01 DK088190/DK/NIDDK NIH HHS; R01 GM093072/GM/NIGMS NIH HHS; R01 GM101171/GM/NIGMS NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Proto-Oncogene Proteins c-myc; 0/Tumor Suppressor Proteins; EC 2.4.2.31/Sirt6 protein, mouse; EC 3.5.1.-/SIRT6 protein, human; EC 3.5.1.-/Sirtuins |
| Comments/Corrections | |
Comment In:
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Cell. 2012 Dec 7;151(6):1155-6
[PMID:
23217699
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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