Document Detail


The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism.
MedLine Citation:
PMID:  23217706     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
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:
Title:  Cell     Volume:  151     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-10     Completed Date:  2013-02-06     Revised Date:  2014-04-28    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1185-99     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
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:
DK088190-01A1/DK/NIDDK NIH HHS; GM093072-01/GM/NIGMS NIH HHS; GM101171/GM/NIGMS NIH HHS; K08 EB012859/EB/NIBIB NIH HHS; P30 AG013283/AG/NIA 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:
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:
Cell. 2012 Dec 7;151(6):1155-6   [PMID:  23217699 ]

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