2. Academic Validation
  3. The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism

The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism

  • Cell. 2012 Dec 7;151(6):1185-99. doi: 10.1016/j.cell.2012.10.047.
Carlos Sebastián 1,  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
Affiliations

Affiliation

  • 1 The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
PMID: 23217706 DOI: 10.1016/j.cell.2012.10.047
Abstract

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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