The IDH-TAU-EGFR triad defines the neovascular landscape of diffuse gliomas
Ricardo Gargini, Berta Segura‐Collar, Beatriz Herránz, Vega García‐Escudero, Andrés Romero‐Bravo, Felipe J. Núñez, Daniel García‐Pérez, Jacqueline Gutiérrez-Guamán, Ángel Ayuso‐Sacido, Joan Seoane, Ángel Pérez‐Núñez, Juan Manuel Sepúlveda-Sánchez, Aurelio Hernández‐Laín, María G. Castro, Ramón García‐Escudero, Jesús Ávila, Pilar Sánchez‐Gómez
Abstract
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.