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Tau, downstream of IDH mut, inhibits the EGFR/NF-kB/TAZ mesenchymal axis, normalizing the vasculature and impairing glioma aggressiveness

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Date
2021-01-22
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Authors
Gargini, Ricardo ; Segura Collar, Berta ; Herránz, Beatriz ; García Escudero, Vega ; Romero Bravo, Andrés ; Núñez, Felipe J. ; García Pérez, Daniel ; Gutiérrez Guamán, Jacqueline ; Ayuso Sacido, Ángel ; Seoane, Joan ; Pérez Núñez, Ángel ; Sepúlveda Sánchez, Juan M. ; Hernández Laín, Aurelio ; Castro, María G. ; García Escudero, Ramón ; Ávila, Jesús ; Sánchez Gómez, Pilar
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Facultades de la UMU::Facultad de Medicina
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Publisher
American Association for the Advancement of Science
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Farmacología
DOI
https://doi.org/10.1126/scitranslmed.aax1501
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info:eu-repo/semantics/article
Description
Abstract
Mutant IDH1/2 gliomas represent a more indolent form of cancer. However, how this group of tumors progress, in a microenvironment-dependent manner, is still a pending question. Here we describe that the expression of Tau, a gene classically associated with neurodegenerative diseases, is epigenetically controlled by the balance between wild-type and mutant IDH1/2 in gliomas. Moreover, Tau is almost absent from tumors with EGFR mutations, whereas its expression is inversely correlated with overall survival in gliomas carrying wild-type or amplified EGFR. We demonstrate that the overexpression of Tau, through the stabilization of microtubules, impairs the mesenchymal/pericyte transformation of EGFRamp/wt glioma cells through the blockade of the EGFR-NFκB-TAZ axis. However, mutant EGFR induces a constitutive activation of this pathway, which is no longer sensitive to Tau. By inhibiting the phenotypic plasticity of EGFRamp/wt glioma cells, Tau protein inhibits angiogenesis and favors vascular normalization, decreasing tumor aggressiveness.
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Tau MAPT , MAPT , EGFR , Microtubule stabilizers , TAZ , NF-kB , Cancer stem cell CSC plasticity , Epithelial to mesenchymal EMT transition , Tumor derived pericytes , Vascular normalization , Tumor microenvironment TME , Glioma
Citation
Science Translational Medicine, 2020, Vol. 12, Issue 527
URI
http://hdl.handle.net/10201/208541
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