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Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/133928
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dc.contributor.authorAguilar, Esther-
dc.contributor.authorZodda, Erika-
dc.contributor.authorMeca-Cortés, Óscar-
dc.contributor.authorDelowar, Hossain-
dc.contributor.authorPons, Mònica-
dc.contributor.authorCelià-Terrassa, Toni-
dc.contributor.authorThomson, Timothy M.-
dc.contributor.authorCascante, Marta-
dc.date.accessioned2016-06-22T11:33:21Z-
dc.date.available2016-06-22T11:33:21Z-
dc.date.issued2016-01-11-
dc.identifierdoi: 10.1002/stem.2286-
dc.identifierissn: 1549-4918-
dc.identifier.citationStem Cells 34(5): 1163-1176 (2016)-
dc.identifier.urihttp://hdl.handle.net/10261/133928-
dc.descriptionEsther Aguilar et al.-
dc.description.abstractIn solid tumors, cancer stem cells (CSCs) can arise independently of epithelial-mesenchymal transition (EMT). In spite of recent efforts, the metabolic reprogramming associated with CSC phenotypes uncoupled from EMT is poorly understood. Here, by using metabolomic and fluxomic approaches, we identify major metabolic profiles that differentiate metastatic prostate epithelial CSCs (e-CSCs) from non-CSCs expressing a stable EMT. We have found that the e-CSC program in our cellular model is characterized by a high plasticity in energy substrate metabolism, including an enhanced Warburg effect, a greater carbon and energy source flexibility driven by fatty acids and amino acid metabolism and an essential reliance on the proton buffering capacity conferred by glutamine metabolism. An analysis of transcriptomic data yielded a metabolic gene signature for our e-CSCs consistent with the metabolomics and fluxomics analyses that correlated with tumor progression and metastasis in prostate cancer and in 11 additional cancer types. Interestingly, an integrated metabolomics, fluxomics, and transcriptomics analysis allowed us to identify key metabolic players regulated at the post-transcriptional level, suggesting potential biomarkers and therapeutic targets to effectively forestall metastasis.-
dc.description.sponsorshipThis work was supported by funds to M.C. from MICINN (SAF2011–25726 and SAF2014-56059-R, European Comission FEDER-Una manera de hacer Europa); Agència Catalana d'Ajuts Universitaris i de Recerca (AGAUR) (2014SGR-1017), ICREA Foundation (Generalitat de Catalunya) and European Commission (Metaflux, PITN-GA-2010-264780); to T.M.T. from MICINN (SAF2011-24686), MINECO (SAF2012-40017-C02-01, European Comission FEDER-Una manera de hacer Europa), AGAUR (2009SGR1482), and Xarxa de Referència en Biotecnologia; and to D.H. and F.M. from NIH (5R01CA158921-02). E.A. was supported by a fellowship from the MECD and a travel grant from RTICC; I.M.M. by a EC Marie Curie grant (Metaflux, PITN-GA-2010-264780)-
dc.publisherAlphaMed Press-
dc.relationinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-56059-R-
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/264780-
dc.rightsclosedAccess-
dc.subjectMitochondrial metabolism-
dc.subjectMetabolic flux analysis-
dc.subjectGlutaminolysis-
dc.subjectWarburg effect-
dc.subjectEpithelial-mesenchymal transition-
dc.subjectCancer stem cells-
dc.titleMetabolic Reprogramming and Dependencies Associated with Epithelial Cancer Stem Cells Independent of the Epithelial-Mesenchymal Transition Program-
dc.typeartículo-
dc.identifier.doi10.1002/stem.2286-
dc.relation.publisherversionhttp://dx.doi.org/10.1002/stem.2286-
dc.date.updated2016-06-22T11:33:21Z-
dc.description.versionPeer Reviewed-
dc.language.rfc3066eng-
dc.contributor.funderMinisterio de Ciencia e Innovación (España)-
dc.contributor.funderNational Institutes of Health (US)-
dc.contributor.funderInstitución Catalana de Investigación y Estudios Avanzados-
dc.contributor.funderGeneralitat de Catalunya-
dc.contributor.funderEuropean Commission-
dc.contributor.funderMinisterio de Economía y Competitividad (España)-
dc.contributor.funderMinisterio de Educación, Cultura y Deporte (España)-
dc.relation.csicSí-
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004837es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100000002es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003741es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100002809es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000780es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003329es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003176es_ES
dc.identifier.pmid27146024-
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.openairetypeartículo-
item.grantfulltextnone-
item.cerifentitytypePublications-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextNo Fulltext-
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