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dc.contributor.authorFreinkman, Elizaveta
dc.contributor.authorComb, William C.
dc.contributor.authorCantor, Jason R.
dc.contributor.authorTam, Wai Leong
dc.contributor.authorThiru, Prathapan
dc.contributor.authorKanarek, Naama
dc.contributor.authorBierie, Brian
dc.contributor.authorShaul, Yoav
dc.contributor.authorKim, Dohoon
dc.contributor.authorChen, Walter W.
dc.contributor.authorPossemato, Richard
dc.contributor.authorReinhardt, Ferenc
dc.contributor.authorWeinberg, Robert A
dc.contributor.authorYaffe, Michael B
dc.contributor.authorSabatini, David
dc.contributor.authorPacold, Michael Edward
dc.date.accessioned2017-06-02T17:24:08Z
dc.date.available2017-06-02T17:24:08Z
dc.date.issued2014-08
dc.date.submitted2014-06
dc.identifier.issn0092-8674
dc.identifier.issn1097-4172
dc.identifier.urihttp://hdl.handle.net/1721.1/109548
dc.description.abstractIt is increasingly appreciated that oncogenic transformation alters cellular metabolism to facilitate cell proliferation, but less is known about the metabolic changes that promote cancer cell aggressiveness. Here, we analyzed metabolic gene expression in cancer cell lines and found that a set of high-grade carcinoma lines expressing mesenchymal markers share a unique 44 gene signature, designated the “mesenchymal metabolic signature” (MMS). A FACS-based shRNA screen identified several MMS genes as essential for the epithelial-mesenchymal transition (EMT), but not for cell proliferation. Dihydropyrimidine dehydrogenase (DPYD), a pyrimidine-degrading enzyme, was highly expressed upon EMT induction and was necessary for cells to acquire mesenchymal characteristics in vitro and for tumorigenic cells to extravasate into the mouse lung. This role of DPYD was mediated through its catalytic activity and enzymatic products, the dihydropyrimidines. Thus, we identify metabolic processes essential for the EMT, a program associated with the acquisition of metastatic and aggressive cancer cell traits.en_US
dc.description.sponsorshipUnited States. National Institutes of Health (RO1 CA103866)en_US
dc.description.sponsorshipUnited States. National Institutes of Health (AI047389)en_US
dc.description.sponsorshipUnited States. National Institutes of Health (K99 CA168940)en_US
dc.description.sponsorshipAmerican Cancer Society (PF-12-099-01-TGB)en_US
dc.description.sponsorshipAmerican Cancer Society (PF-13-356-01-TBE)en_US
dc.description.sponsorshipUnited States. Department of Defense (BC123066)en_US
dc.description.sponsorshipUnited States. National Institutes of Health (CA112967)en_US
dc.description.sponsorshipUnited States. National Institutes of Health (ES015339)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.cell.2014.07.032en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleDihydropyrimidine Accumulation Is Required for the Epithelial-Mesenchymal Transitionen_US
dc.typeArticleen_US
dc.identifier.citationShaul, Yoav D.; Freinkman, Elizaveta; Comb, William C.; Cantor, Jason R.; Tam, Wai Leong; Thiru, Prathapan; Kim, Dohoon et al. “Dihydropyrimidine Accumulation Is Required for the Epithelial-Mesenchymal Transition.” Cell 158, no. 5 (August 2014): 1094–1109 © 2014 Elsevier Incen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentWhitehead Institute for Biomedical Researchen_US
dc.contributor.departmentLudwig Center for Molecular Oncology (Massachusetts Institute of Technology)en_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorShaul, Yoav
dc.contributor.mitauthorKim, Dohoon
dc.contributor.mitauthorPacold, Michael E
dc.contributor.mitauthorChen, Walter W.
dc.contributor.mitauthorPossemato, Richard
dc.contributor.mitauthorReinhardt, Ferenc
dc.contributor.mitauthorWeinberg, Robert A
dc.contributor.mitauthorYaffe, Michael B
dc.contributor.mitauthorSabatini, David
dc.relation.journalCellen_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.orderedauthorsShaul, Yoav D.; Freinkman, Elizaveta; Comb, William C.; Cantor, Jason R.; Tam, Wai Leong; Thiru, Prathapan; Kim, Dohoon; Kanarek, Naama; Pacold, Michael E.; Chen, Walter W.; Bierie, Brian; Possemato, Richard; Reinhardt, Ferenc; Weinberg, Robert A.; Yaffe, Michael B.; Sabatini, David M.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0003-3688-2378
dc.identifier.orcidhttps://orcid.org/0000-0002-7043-5013
dc.identifier.orcidhttps://orcid.org/0000-0002-2401-0030
dc.identifier.orcidhttps://orcid.org/0000-0002-0895-3557
dc.identifier.orcidhttps://orcid.org/0000-0002-9547-3251
dc.identifier.orcidhttps://orcid.org/0000-0002-1446-7256
mit.licensePUBLISHER_CCen_US


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