The Histone Deacetylase SIRT6 Is a Tumor Suppressor that Controls Cancer Metabolism
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Sebastián-2012-The Histone Deacetyl.pdf
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Author(s)
Zwaans, Bernadette M.M.
Silberman, Dafne M.
Goren, Alon
Zhong, Lei
Ram, Oren
Truelove, Jessica
Guimaraes, Alexander R.
Toiber, Debra
Cosentino, Claudia
Greenson, Joel K.
Date Issued
December 2012
Journal
Cell
Publisher
Elsevier
Citation
Sebastian, Carlos, Bernadette M.M. Zwaans, Dafne M. Silberman, Melissa Gymrek, Alon Goren, Lei Zhong, Oren Ram, et al. “The Histone Deacetylase SIRT6 Is a Tumor Suppressor That Controls Cancer Metabolism.” Cell 151, no. 6 (December 2012): 1185–1199. © 2012 Elsevier Inc.
Version
Final published version
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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.cell.2012.10.047
