dc.contributor.author | Zwaans, Bernadette M.M. | |
dc.contributor.author | Silberman, Dafne M. | |
dc.contributor.author | Goren, Alon | |
dc.contributor.author | Zhong, Lei | |
dc.contributor.author | Ram, Oren | |
dc.contributor.author | Truelove, Jessica | |
dc.contributor.author | Guimaraes, Alexander R. | |
dc.contributor.author | Toiber, Debra | |
dc.contributor.author | Cosentino, Claudia | |
dc.contributor.author | Greenson, Joel K. | |
dc.contributor.author | MacDonald, Alasdair I. | |
dc.contributor.author | McGlynn, Liane | |
dc.contributor.author | Maxwell, Fraser | |
dc.contributor.author | Edwards, Joanne | |
dc.contributor.author | Giacosa, Sofia | |
dc.contributor.author | Guccione, Ernesto | |
dc.contributor.author | Weissleder, Ralph | |
dc.contributor.author | Bernstein, Bradley E. | |
dc.contributor.author | Regev, Aviv | |
dc.contributor.author | Shiels, Paul G. | |
dc.contributor.author | Lombard, David B. | |
dc.contributor.author | Mostoslavsky, Raul | |
dc.contributor.author | Sebastian, Carlos | |
dc.contributor.author | Gymrek, Melissa A. | |
dc.contributor.author | Bernstein, Bradley E. | |
dc.date.accessioned | 2014-11-12T13:47:30Z | |
dc.date.available | 2014-11-12T13:47:30Z | |
dc.date.issued | 2012-12 | |
dc.date.submitted | 2012-08 | |
dc.identifier.issn | 00928674 | |
dc.identifier.issn | 1097-4172 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/91526 | |
dc.description.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. | en_US |
dc.description.sponsorship | American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowship | en_US |
dc.description.sponsorship | National Human Genome Research Institute (U.S.). Center of Excellence in Genome Science (Grant P50HG006193) | en_US |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1016/j.cell.2012.10.047 | en_US |
dc.rights | 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. | en_US |
dc.source | Elsevier | en_US |
dc.title | The Histone Deacetylase SIRT6 Is a Tumor Suppressor that Controls Cancer Metabolism | en_US |
dc.type | Article | en_US |
dc.identifier.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. | en_US |
dc.contributor.department | Harvard University--MIT Division of Health Sciences and Technology | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Whitehead Institute for Biomedical Research | en_US |
dc.contributor.mitauthor | Gymrek, Melissa A. | en_US |
dc.contributor.mitauthor | Bernstein, Bradley E. | en_US |
dc.contributor.mitauthor | Regev, Aviv | en_US |
dc.relation.journal | Cell | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Sebastian, Carlos; Zwaans, Bernadette M.M.; Silberman, Dafne M.; Gymrek, Melissa; Goren, Alon; Zhong, Lei; Ram, Oren; Truelove, Jessica; Guimaraes, Alexander R.; Toiber, Debra; Cosentino, Claudia; Greenson, Joel K.; MacDonald, Alasdair I.; McGlynn, Liane; Maxwell, Fraser; Edwards, Joanne; Giacosa, Sofia; Guccione, Ernesto; Weissleder, Ralph; Bernstein, Bradley E.; Regev, Aviv; Shiels, Paul G.; Lombard, David B.; Mostoslavsky, Raul | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-8567-2049 | |
dc.identifier.orcid | https://orcid.org/0000-0002-6086-3903 | |
mit.license | PUBLISHER_POLICY | en_US |
mit.metadata.status | Complete | |