Browsing by Subject "Tumor microenvironment TME"

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    Tau, downstream of IDH mut, inhibits the EGFR/NF-kB/TAZ mesenchymal axis, normalizing the vasculature and impairing glioma aggressiveness
    (American Association for the Advancement of Science, 2021-01-22) 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; Farmacología; Facultades de la UMU::Facultad de Medicina
    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.