IDH-Tau-EGFR triad defines the neovascular landscape of diffuse gliomas by controlling mesenchymal differentiation
Felipe J. Núñez,
Juan M. Sepúlveda-Sánchez,
María G. Castro,
Posted 07 Feb 2019
bioRxiv DOI: 10.1101/541326
Posted 07 Feb 2019
Mutant IDH1/2 gliomas represent a more indolent form of cancer. However, how this group of tumors evolve, 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, the level of Tau decreases when the tumor progresses. Besides, 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. Here, we demonstrate that the overexpression of Tau, through the stabilization of microtubules, impairs the mesenchymal/pericyte-like transformation of glioma cells by blocking 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 and rendering the tumors more sensitive to chemotherapy. One Sentence Summary Tau, which is induced by IDH mutations, inhibits the EGFR/NF-kB/TAZ axis and impairs the mesenchymal/pericyte-like transformation of glioma cells, normalizing the vasculature and impairing tumor aggressiveness.
- Downloaded 681 times
- Download rankings, all-time:
- Site-wide: 31,405
- In cancer biology: 855
- Year to date:
- Site-wide: 75,542
- Since beginning of last month:
- Site-wide: 59,195
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!