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dc.contributor.authorPozo, Natividad 
dc.contributor.authorZahonero, Cristina 
dc.contributor.authorFernández, Paloma
dc.contributor.authorLiñares, Jose M
dc.contributor.authorAyuso, Angel
dc.contributor.authorHagiwara, Masatoshi
dc.contributor.authorPérez, Angel
dc.contributor.authorRicoy, Jose R
dc.contributor.authorHernández-Laín, Aurelio
dc.contributor.authorSepúlveda, Juan M
dc.contributor.authorSanchez-Gomez, Pilar 
dc.date.accessioned2020-04-23T17:10:17Z
dc.date.available2020-04-23T17:10:17Z
dc.date.issued2013-06
dc.identifier.citationJ Clin Invest. 2013 Jun;123(6):2475-87.es_ES
dc.identifier.issn0021-9738es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/9727
dc.description.abstractGlioblastomas (GBMs) are very aggressive tumors that are resistant to conventional chemo- and radiotherapy. New molecular therapeutic strategies are required to effectively eliminate the subpopulation of GBM tumor-initiating cells that are responsible for relapse. Since EGFR is altered in 50% of GBMs, it represents one of the most promising targets; however, EGFR kinase inhibitors have produced poor results in clinical assays, with no clear explanation for the observed resistance. We uncovered a fundamental role for the dual-specificity tyrosine phosphorylation-regulated kinase, DYRK1A, in regulating EGFR in GBMs. We found that DYRK1A was highly expressed in these tumors and that its expression was correlated with that of EGFR. Moreover, DYRK1A inhibition promoted EGFR degradation in primary GBM cell lines and neural progenitor cells, sharply reducing the self-renewal capacity of normal and tumorigenic cells. Most importantly, our data suggest that a subset of GBMs depends on high surface EGFR levels, as DYRK1A inhibition compromised their survival and produced a profound decrease in tumor burden. We propose that the recovery of EGFR stability is a key oncogenic event in a large proportion of gliomas and that pharmacological inhibition of DYRK1A could represent a promising therapeutic intervention for EGFR-dependent GBMs.es_ES
dc.description.sponsorshipThis work was supported by grants from the Ministerio de Educación y Ciencia (MEC; SAF2008-04531), the Ministerio de Ciencia e Innovación (MICINN, PLE2009-0115), and the Ministerio de Asuntos Exteriores y Cooperación (MAEC-AECID A/023963/09; to P. Sánchez-Gómez), as well as by grants from the Fondo de Investigación Sanitaria (FIS-PS09-01977) and Fundación Mutua-madrileña grants (FMM 2007/057, to J.R. Ricoy; and FMM2011/89, to J.M. Sepúlveda).es_ES
dc.language.isoenges_ES
dc.publisherAmerican Society for Clinical Investigationes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimals es_ES
dc.subject.meshAntineoplastic Agents es_ES
dc.subject.meshBrain Neoplasms es_ES
dc.subject.meshCell Line, Tumor es_ES
dc.subject.meshCell Proliferation es_ES
dc.subject.meshCell Survival es_ES
dc.subject.meshErbB Receptors es_ES
dc.subject.meshGene Expression es_ES
dc.subject.meshGene Knockdown Techniques es_ES
dc.subject.meshGlioblastoma es_ES
dc.subject.meshHarmine es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Nude es_ES
dc.subject.meshNeoplastic Stem Cells es_ES
dc.subject.meshNeural Stem Cells es_ES
dc.subject.meshProtein Stability es_ES
dc.subject.meshProtein-Serine-Threonine Kinases es_ES
dc.subject.meshProtein-Tyrosine Kinases es_ES
dc.subject.meshProteolysis es_ES
dc.subject.meshRNA, Small Interfering es_ES
dc.subject.meshSignal Transduction es_ES
dc.subject.meshSpheroids, Cellular es_ES
dc.subject.meshTumor Burden es_ES
dc.subject.meshXenograft Model Antitumor Assays es_ES
dc.titleInhibition of DYRK1A destabilizes EGFR and reduces EGFR-dependent glioblastoma growthes_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID23635774es_ES
dc.format.volume123es_ES
dc.format.number6es_ES
dc.format.page2475-87es_ES
dc.identifier.doi10.1172/JCI63623es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España)
dc.contributor.funderMinisterio de Educación y Ciencia (España)
dc.contributor.funderMinisterio de Asuntos Exteriores y Cooperación (España)
dc.contributor.funderFondo de Investigaciones Sanitarias
dc.contributor.funderFundación Mutua Madrileña Automovilista
dc.description.peerreviewedes_ES
dc.identifier.e-issn1558-8238es_ES
dc.relation.publisherversionhttps://doi.org/10.1172/JCI63623es_ES
dc.identifier.journalThe Journal of clinical investigationes_ES
dc.repisalud.centroISCIII::Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC)es_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/MEC; SAF2008-04531es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/MICINN, PLE2009-0115es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/MAEC-AECID A/023963/09es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/FIS-PS09-01977es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/FMM 2007/057es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/FMM2011/89es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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Atribución-NoComercial-CompartirIgual 4.0 Internacional
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