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dc.contributor.authorBirsoy, Kivanc
dc.contributor.authorWang, Tim
dc.contributor.authorPossemato, Richard
dc.contributor.authorKoch, Catherine E.
dc.contributor.authorChen, Walter W.
dc.contributor.authorHutchins, Amanda W.
dc.contributor.authorGultekin, Yetis
dc.contributor.authorCarette, Jan E.
dc.contributor.authorBrummelkamp, Thijn R.
dc.contributor.authorClish, Clary
dc.contributor.authorYilmaz, Omer
dc.contributor.authorPeterson, Timothy Richard
dc.contributor.authorSabatini, David
dc.date.accessioned2013-07-10T14:30:10Z
dc.date.available2013-07-10T14:30:10Z
dc.date.issued2012-12
dc.date.submitted2012-07
dc.identifier.issn1061-4036
dc.identifier.issn1546-1718
dc.identifier.urihttp://hdl.handle.net/1721.1/79435
dc.description.abstractThere is increasing evidence that oncogenic transformation modifies the metabolic program of cells. A common alteration is the upregulation of glycolysis, and efforts to target glycolytic enzymes for anticancer therapy are under way. Here, we performed a genome-wide haploid genetic screen to identify resistance mechanisms to 3-bromopyruvate (3-BrPA), a drug candidate that inhibits glycolysis in a poorly understood fashion. We identified the SLC16A1 gene product, MCT1, as the main determinant of 3-BrPA sensitivity. MCT1 is necessary and sufficient for 3-BrPA uptake by cancer cells. Additionally, SLC16A1 mRNA levels are the best predictor of 3-BrPA sensitivity and are most elevated in glycolytic cancer cells. Furthermore, forced MCT1 expression in 3-BrPA–resistant cancer cells sensitizes tumor xenografts to 3-BrPA treatment in vivo. Our results identify a potential biomarker for 3-BrPA sensitivity and provide proof of concept that the selectivity of cancer-expressed transporters can be exploited for delivering toxic molecules to tumors.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH CA103866)en_US
dc.description.sponsorshipJane Coffin Childs Memorial Fund for Medical Research (Fellowship)en_US
dc.description.sponsorshipNational Science Foundation (U.S.) (Fellowship)en_US
dc.description.sponsorshipHoward Hughes Medical Institute (Investigator)en_US
dc.language.isoen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/ng.2471en_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.sourceSabatini via Courtney Crummetten_US
dc.titleMCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumorsen_US
dc.typeArticleen_US
dc.identifier.citationBirsoy, Kivanç, Tim Wang, Richard Possemato, Omer H Yilmaz, Catherine E Koch, Walter W Chen, Amanda W Hutchins, et al. MCT1-mediated Transport of a Toxic Molecule Is an Effective Strategy for Targeting Glycolytic Tumors. Nature Genetics 45, no. 1 (December 2, 2012): 104-108.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.approverSabatini, David M.en_US
dc.contributor.mitauthorSabatini, David M.en_US
dc.contributor.mitauthorBirsoy, Kivancen_US
dc.contributor.mitauthorWang, Timen_US
dc.contributor.mitauthorPossemato, Richarden_US
dc.contributor.mitauthorYilmaz, Omer H.en_US
dc.contributor.mitauthorKoch, Catherine E.en_US
dc.contributor.mitauthorChen, Walter W.en_US
dc.contributor.mitauthorHutchins, Amanda W.en_US
dc.contributor.mitauthorGultekin, Yetisen_US
dc.contributor.mitauthorPeterson, Tim R.en_US
dc.relation.journalNature Geneticsen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsBirsoy, Kivanç; Wang, Tim; Possemato, Richard; Yilmaz, Omer H; Koch, Catherine E; Chen, Walter W; Hutchins, Amanda W; Gultekin, Yetis; Peterson, Tim R; Carette, Jan E; Brummelkamp, Thijn R; Clish, Clary B; Sabatini, David Men_US
dc.identifier.orcidhttps://orcid.org/0000-0002-4227-5163
dc.identifier.orcidhttps://orcid.org/0000-0002-2401-0030
dc.identifier.orcidhttps://orcid.org/0000-0002-7043-5013
dc.identifier.orcidhttps://orcid.org/0000-0002-7577-4612
dc.identifier.orcidhttps://orcid.org/0000-0002-1446-7256
dc.identifier.orcidhttps://orcid.org/0000-0002-1751-7327
mit.licensePUBLISHER_POLICYen_US


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