2026-06-14T03:45:05Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/271592026-01-20T01:21:07Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19617
Repisalud author Gargini, Ricardo author Sánchez-Gómez, Pilar author Segura-Collar, Berta author Herránz, Beatriz author García-Escudero, Vega author Romero-Bravo, Andrés author Núñez, Felipe J author García-Pérez, Daniel author Gutiérrez-Guamán, Jacqueline author Ayuso-Sacido, Angel author Seoane, Joan author Pérez-Núñez, Angel author Sepúlveda-Sánchez, Juan M author Hernández-Laín, Aurelio author Castro, María G author García-Escudero, Ramón author Ávila, Jesús author Sánchez-Gómez, Pilar 2026-01-19T13:57:02Z 2026-01-19T13:57:02Z 2020-01-22 Gargini R, Segura-Collar B, Herránz B, García-Escudero V, Romero-Bravo A, Núñez FJ, García-Pérez D, Gutiérrez-Guamán J, Ayuso-Sacido A, Seoane J, Pérez-Núñez A, Sepúlveda-Sánchez JM, Hernández-Laín A, Castro MG, García-Escudero R, Ávila J, Sánchez-Gómez P. The IDH-TAU-EGFR triad defines the neovascular landscape of diffuse gliomas. Sci Transl Med. 2020 Jan 22;12(527):eaax1501. doi: 10.1126/scitranslmed.aax1501. PMID: 31969485; PMCID: PMC7055928. 10.1126/scitranslmed.aax1501 Science Translational Medicine 31969485 https://hdl.handle.net/20.500.12105/27159 Gliomas 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 (), 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, was almost absent from tumors with epidermal growth factor receptor () mutations, whereas its trancription negatively correlated with overall survival in gliomas carrying wt or amplified (amp) 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. eng The IDH-TAU-EGFR triad defines the neovascular landscape of diffuse gliomas. research article 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 URL https://repisalud.isciii.es/bitstreams/896efe98-f101-4c49-9cf3-df50206fddd1/download File MD5 f348ed5edefadbe36a8fb581a5869503 3101308 application/pdf IDH_Tau_EGFR_Triad_2020.pdf URL https://repisalud.isciii.es/bitstreams/e0ca2d94-5e82-439b-b43a-a29ce5d6f5cb/download File MD5 25148edf4fb16ab9af85024ccb758eba 3170360 application/pdf Supplementary_IDH_Tau_EGFR_Triad_2020.pdf URL https://repisalud.isciii.es/bitstreams/216d06aa-b533-4b16-85b0-0c12c27251b0/download File MD5 76c1e9d333e7f0c2ae8b786bd40c9e17 54512 application/zip Supplementary_IDH_Tau_EGFR_Triad_2020.zip