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dc.contributor.authorTalamillo Cancelo, Canaes_ES
dc.contributor.authorGrande González, Laraes_ES
dc.contributor.authorRuiz Ontañón, Patriciaes_ES
dc.contributor.authorVelásquez Rodríguez, Carlos José es_ES
dc.contributor.authorMollinedo, Pilares_ES
dc.contributor.authorTorices del Val, Silviaes_ES
dc.contributor.authorSánchez Gómez, Pilares_ES
dc.contributor.authorAznar, Ángelaes_ES
dc.contributor.authorEsparis Ogando, Azucenaes_ES
dc.contributor.authorLópez López, Carloses_ES
dc.contributor.authorLafita Navarro, María Carmenes_ES
dc.contributor.authorBerciano Blanco, María Teresa es_ES
dc.contributor.authorMontero Simón, Juan Antonio es_ES
dc.contributor.authorVázquez Barquero, Alfonso es_ES
dc.contributor.authorSegura, Víctores_ES
dc.contributor.authorVillagra, Nuria T.es_ES
dc.contributor.authorPandiella, Atanasioes_ES
dc.contributor.authorLafarga Coscojuela, Miguel Ángel es_ES
dc.contributor.authorLeón Serrano, Javier es_ES
dc.contributor.authorMartínez Climent, José A.es_ES
dc.contributor.authorSanz Moreno, Victoriaes_ES
dc.contributor.authorFernández Luna, José Luis es_ES
dc.contributor.otherUniversidad de Cantabriaes_ES
dc.date.accessioned2017-05-23T18:15:16Z
dc.date.available2017-05-23T18:15:16Z
dc.date.issued2016-09-19es_ES
dc.identifier.issn0950-9232es_ES
dc.identifier.issn1476-5594es_ES
dc.identifier.urihttp://hdl.handle.net/10902/11051
dc.description.abstractLong-term survival remains low for most patients with glioblastoma (GBM), which reveals the need for markers of disease outcome and novel therapeutic targets. We describe that ODZ1 (also known as TENM1), a type II transmembrane protein involved in fetal brain development, plays a crucial role in the invasion of GBM cells. Differentiation of glioblastoma stem-like cells drives the nuclear translocation of an intracellular fragment of ODZ1 through proteolytic cleavage by signal peptide peptidase-like 2a. The intracellular fragment of ODZ1 promotes cytoskeletal remodelling of GBM cells and invasion of the surrounding environment both in vitro and in vivo. Absence of ODZ1 by gene deletion or downregulation of ODZ1 by small interfering RNAs drastically reduces the invasive capacity of GBM cells. This activity is mediated by an ODZ1-triggered transcriptional pathway, through the E-box binding Myc protein, that promotes the expression and activation of Ras homolog family member A (RhoA) and subsequent activation of Rho-associated, coiled-coil containing protein kinase (ROCK). Overexpression of ODZ1 in GBM cells reduced survival of xenografted mice. Consistently, analysis of 122 GBM tumour samples revealed that the number of ODZ1-positive cells inversely correlated with overall and progression-free survival. Our findings establish a novel marker of invading GBM cells and consequently a potential marker of disease progression and a therapeutic target in GBM.es_ES
dc.language.isoenges_ES
dc.publisherBasingstoke : Nature Publishing Groupes_ES
dc.rights©Macmillan Publishers Limited, part of Springer Naturees_ES
dc.sourceOncogene. 2017 Mar 23;36(12):1733-1744es_ES
dc.titleODZ1 allows glioblastoma to sustain invasiveness through a Myc-dependent transcriptional upregulation of RhoAes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.accessRightsopenAccesses_ES
dc.identifier.DOI10.1038/onc.2016.341es_ES
dc.type.versionacceptedVersiones_ES


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