El papel de la histona desacetilasa 6 en el desarrollo del gioblastoma
- Autores: Alejandro Urdiciain Ezpeleta
- Directores de la Tesis: Francisco Javier Sáez Castresana (dir. tes.)
- Lectura: En la Universidad de Navarra ( España ) en 2020
- Idioma: español
- Tribunal Calificador de la Tesis: Adolfo López de Munain Arregui (presid.), Eduardo Ansorena Artieda (secret.), Jaime Gállego (voc.), Miguel Angel Barajas Vélez (voc.), Cristina Montiel Duarte (voc.)
- Programa de doctorado: Programa de Doctorado en Medicina Aplicada y Biomedicina por la Universidad de Navarra
- Materias:
- Enlaces
- Tesis en acceso abierto en: Dadun
- Resumen
Glioblastoma multiforme, the most common type of malignant brain tumor as well as the most aggressive one, lacks an effective therapy. Glioblastoma presents overexpression of mesenchymal markers Snail, Slug and N-Cadherin, and of the autophagic marker p62. Glioblastoma cell lines also present an increased autophagic flux, overexpression of mesenchymal markers, Shh pathway activation and lack of primary cilia. In this study, we aimed to evaluate the role of histone deacetylase 6 (HDAC6) in the development of glioblastoma, as HDAC6 is the most overexpressed of all HDACs isoforms in this tumor. We treated glioblastoma cell lines with siHDAC6 and tubastatin A, a HDAC6 inhibitor. Both treatments inhibited proliferation, migration and clonogenicity of glioblastoma cell lines. They also reversed the mesenchymal phenotype, decreased the autophagic flux, inhibited Shh pathway and recovered the expression of primary cilia in glioblastoma cell lines. The treatment of tubastatin A also sensitized glioblastoma cell lines to temozolomide treatment, the chemotherapeutic agent used against glioblastoma. These results demonstrate that HDAC6 might be a good target for glioblastoma treatment.
