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dc.contributor.authorGarcia-Cao, Isabel
dc.contributor.authorSong, Min Sup
dc.contributor.authorHobbs, Robin M.
dc.contributor.authorLaurent, Gaelle
dc.contributor.authorGiorgi, Carlotta
dc.contributor.authorde Boer, Vincent C. J.
dc.contributor.authorAnastasiou, Dimitrios
dc.contributor.authorIto, Keisuke
dc.contributor.authorSasaki, Atsuo T.
dc.contributor.authorRameh, Lucia
dc.contributor.authorCarracedo, Arkaitz
dc.contributor.authorVander Heiden, Matthew G.
dc.contributor.authorCantley, Lewis C.
dc.contributor.authorPinton, Paolo
dc.contributor.authorHaigis, Marcia C.
dc.contributor.authorPandolfi, Pier Paolo
dc.contributor.authorVander Heiden, Matthew G.
dc.date.accessioned2014-02-27T17:38:52Z
dc.date.available2014-02-27T17:38:52Z
dc.date.issued2012-03
dc.date.submitted2011-11
dc.identifier.issn00928674
dc.identifier.urihttp://hdl.handle.net/1721.1/85109
dc.description.abstractDecremental loss of PTEN results in cancer susceptibility and tumor progression. PTEN elevation might therefore be an attractive option for cancer prevention and therapy. We have generated several transgenic mouse lines with PTEN expression elevated to varying levels by taking advantage of bacterial artificial chromosome (BAC)-mediated transgenesis. The “Super-PTEN” mutants are viable and show reduced body size due to decreased cell number, with no effect on cell size. Unexpectedly, PTEN elevation at the organism level results in healthy metabolism characterized by increased energy expenditure and reduced body fat accumulation. Cells derived from these mice show reduced glucose and glutamine uptake and increased mitochondrial oxidative phosphorylation and are resistant to oncogenic transformation. Mechanistically we find that PTEN elevation orchestrates this metabolic switch by regulating PI3K-dependent and -independent pathways and negatively impacting two of the most pronounced metabolic features of tumor cells: glutaminolysis and the Warburg effect.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH grant R01 CA-82328-09)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH grant P01-CA089021)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH grant R01-GM41890)en_US
dc.description.sponsorshipItalian Association for Cancer Research (grant)en_US
dc.description.sponsorshipSpain. Ministerio de Educación y Cienciaen_US
dc.description.sponsorshipHuman Frontier Science Program (Strasbourg, France) (Fellowships)en_US
dc.language.isoen_US
dc.publisherElsevier B.V.en_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.cell.2012.02.030en_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.sourceElsevier Open Archiveen_US
dc.titleSystemic Elevation of PTEN Induces a Tumor-Suppressive Metabolic Stateen_US
dc.typeArticleen_US
dc.identifier.citationGarcia-Cao, Isabel, Min Sup Song, Robin M. Hobbs, Gaelle Laurent, Carlotta Giorgi, Vincent C.J. de Boer, Dimitrios Anastasiou, Keisuke Ito, Atsuo T. Sasaki, Lucia Rameh, Arkaitz Carracedo, Matthew G. Vander Heiden, Lewis C. Cantley, Paolo Pinton, Marcia C. Haigis, Pier Paolo Pandolfi. "Systemic Elevation of PTEN Induces a Tumor-Suppressive Metabolic State." Cell, 149.1 (2012): 49-62.© 2012 Elsevier Inc.en_US
dc.contributor.departmentDavid H. Koch Institute for Integrative Cancer Research at MITen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.mitauthorVander Heiden, Matthew G.en_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.orderedauthorsGarcia-Cao, Isabel; Song, Min Sup; Hobbs, Robin M.; Laurent, Gaelle; Giorgi, Carlotta; de Boer, Vincent C.J.; Anastasiou, Dimitrios; Ito, Keisuke; Sasaki, Atsuo T.; Rameh, Lucia; Carracedo, Arkaitz; Vander Heiden, Matthew G.; Cantley, Lewis C.; Pinton, Paolo; Haigis, Marcia C.; Pandolfi, Pier Paoloen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-6702-4192
mit.licensePUBLISHER_POLICYen_US


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