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dc.contributor.authorZwaans, Bernadette M.M.
dc.contributor.authorSilberman, Dafne M.
dc.contributor.authorGoren, Alon
dc.contributor.authorZhong, Lei
dc.contributor.authorRam, Oren
dc.contributor.authorTruelove, Jessica
dc.contributor.authorGuimaraes, Alexander R.
dc.contributor.authorToiber, Debra
dc.contributor.authorCosentino, Claudia
dc.contributor.authorGreenson, Joel K.
dc.contributor.authorMacDonald, Alasdair I.
dc.contributor.authorMcGlynn, Liane
dc.contributor.authorMaxwell, Fraser
dc.contributor.authorEdwards, Joanne
dc.contributor.authorGiacosa, Sofia
dc.contributor.authorGuccione, Ernesto
dc.contributor.authorWeissleder, Ralph
dc.contributor.authorBernstein, Bradley E.
dc.contributor.authorRegev, Aviv
dc.contributor.authorShiels, Paul G.
dc.contributor.authorLombard, David B.
dc.contributor.authorMostoslavsky, Raul
dc.contributor.authorSebastian, Carlos
dc.contributor.authorGymrek, Melissa A.
dc.contributor.authorBernstein, Bradley E.
dc.date.accessioned2014-11-12T13:47:30Z
dc.date.available2014-11-12T13:47:30Z
dc.date.issued2012-12
dc.date.submitted2012-08
dc.identifier.issn00928674
dc.identifier.issn1097-4172
dc.identifier.urihttp://hdl.handle.net/1721.1/91526
dc.description.abstractReprogramming 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.sponsorshipAmerican Society for Engineering Education. National Defense Science and Engineering Graduate Fellowshipen_US
dc.description.sponsorshipNational Human Genome Research Institute (U.S.). Center of Excellence in Genome Science (Grant P50HG006193)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.cell.2012.10.047en_US
dc.rightsArticle 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.sourceElsevieren_US
dc.titleThe Histone Deacetylase SIRT6 Is a Tumor Suppressor that Controls Cancer Metabolismen_US
dc.typeArticleen_US
dc.identifier.citationSebastian, 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.departmentHarvard University--MIT Division of Health Sciences and Technologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentWhitehead Institute for Biomedical Researchen_US
dc.contributor.mitauthorGymrek, Melissa A.en_US
dc.contributor.mitauthorBernstein, Bradley E.en_US
dc.contributor.mitauthorRegev, Aviven_US
dc.relation.journalCellen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsSebastian, 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, Raulen_US
dc.identifier.orcidhttps://orcid.org/0000-0001-8567-2049
dc.identifier.orcidhttps://orcid.org/0000-0002-6086-3903
mit.licensePUBLISHER_POLICYen_US
mit.metadata.statusComplete


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