The IDH-TAU-EGFR triad defines the neovascular landscape of diffuse gliomas.

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dc.contributor.authorGargini, Ricardo
dc.contributor.authorSegura Collar, Berta
dc.contributor.authorHerranz Sánchez, Beatriz
dc.contributor.authorGarcía-Escudero, Vega
dc.contributor.authorRomero Bravo, Andrés
dc.contributor.authorNúñez, Felipe J.
dc.contributor.authorGarcía Pérez, Daniel
dc.contributor.authorGutiérrez-Guamán, Jacqueline
dc.contributor.authorAyuso Sacido, Ángel
dc.contributor.authorSeoane, Joan
dc.contributor.authorPérez Núñez, Ángel
dc.contributor.authorSepúlveda-Sánchez, Juan M.
dc.contributor.authorHernández Laín, Aurelio
dc.contributor.authorG. Castro, María
dc.contributor.authorGarcía Escudero, Ramón
dc.contributor.authorÁvila, Jesús
dc.contributor.authorSánchez Gómez, Pilar
dc.date.accessioned2020-02-10T12:14:13Z
dc.date.available2020-02-10T12:14:13Z
dc.date.issued2020
dc.description.abstractGliomas that express the mutated isoforms of isocitrate dehydrogenase 1/2 (IDH1/2) have better prognosis than wild-type (wt) IDH1/2 gliomas. However, how these mutant (mut) proteins affect the tumor microenvironment is still a pending question. Here, we describe that the transcription of microtubule-associated protein TAU (MAPT), a gene that has been classically associated with neurodegenerative diseases, is epigenetically controlled by the balance between wt and mut IDH1/2 in mouse and human gliomas. In IDH1/2 mut tumors, we found high expression of TAU that decreased with tumor progression. Furthermore, MAPT was almost absent from tumors with epidermal growth factor receptor (EGFR) mutations, whereas its trancription negatively correlated with overall survival in gliomas carrying wt or amplified (amp) EGFR. We demonstrated that the overexpression of TAU, through the stabilization of microtubules, impaired the mesenchymal/pericyte-like transformation of glioma cells by blocking EGFR, nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) and the transcriptional coactivator with PDZ-binding motif (TAZ). Our data also showed that mut EGFR induced a constitutive activation of this pathway, which was no longer sensitive to TAU. By inhibiting the transdifferentiation capacity of EGFRamp/wt tumor cells, TAU protein inhibited angiogenesis and favored vascular normalization, decreasing glioma aggressiveness and increasing their sensitivity to chemotherapy.spa
dc.description.extent772 KBspa
dc.identifier.doi10.1126/scitranslmed.aax1501spa
dc.identifier.issn1946-6234spa
dc.identifier.urihttp://hdl.handle.net/10641/1853
dc.language.isoengspa
dc.publisherScience Translational Medicinespa
dc.relation.publisherversionhttps://stm.sciencemag.org/content/12/527/eaax1501spa
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 España*
dc.rights.accessRightsopen accessspa
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/*
dc.titleThe IDH-TAU-EGFR triad defines the neovascular landscape of diffuse gliomas.spa
dc.typejournal articlespa
dc.type.hasVersionAMspa
dspace.entity.typePublication

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