El papel de la histona desacetilasa 6 en el desarrollo del gioblastoma
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 inc...
| Main Authors: | , |
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| Format: | info:eu-repo/semantics/doctoralThesis |
| Language: | spa |
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Universidad de Navarra
2021
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10171/61042 |
| _version_ | 1793400555688689664 |
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| author | Urdiciain-Ezpeleta, A. (Alejandro) Saez-Castresana, J. (Javier) |
| author_facet | Urdiciain-Ezpeleta, A. (Alejandro) Saez-Castresana, J. (Javier) |
| author_sort | Urdiciain-Ezpeleta, A. (Alejandro) |
| collection | DSpace |
| description | 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. |
| format | info:eu-repo/semantics/doctoralThesis |
| id | oai:dadun.unav.edu:10171-61042 |
| institution | Universidad de Navarra |
| language | spa |
| publishDate | 2021 |
| publisher | Universidad de Navarra |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-610422021-07-07T01:02:24Z El papel de la histona desacetilasa 6 en el desarrollo del gioblastoma Urdiciain-Ezpeleta, A. (Alejandro) Saez-Castresana, J. (Javier) Materias Investigacion::Ciencias de la Salud::Oncología Ciencias clínicas 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. 2021-07-06T09:04:41Z 2021-07-06T09:04:41Z 2021-07-06 2020-12-11 info:eu-repo/semantics/doctoralThesis https://hdl.handle.net/10171/61042 spa info:eu-repo/semantics/embargoedAccess application/pdf Universidad de Navarra |
| spellingShingle | Materias Investigacion::Ciencias de la Salud::Oncología Ciencias clínicas Urdiciain-Ezpeleta, A. (Alejandro) Saez-Castresana, J. (Javier) El papel de la histona desacetilasa 6 en el desarrollo del gioblastoma |
| title | El papel de la histona desacetilasa 6 en el desarrollo del gioblastoma |
| title_full | El papel de la histona desacetilasa 6 en el desarrollo del gioblastoma |
| title_fullStr | El papel de la histona desacetilasa 6 en el desarrollo del gioblastoma |
| title_full_unstemmed | El papel de la histona desacetilasa 6 en el desarrollo del gioblastoma |
| title_short | El papel de la histona desacetilasa 6 en el desarrollo del gioblastoma |
| title_sort | el papel de la histona desacetilasa 6 en el desarrollo del gioblastoma |
| topic | Materias Investigacion::Ciencias de la Salud::Oncología Ciencias clínicas |
| url | https://hdl.handle.net/10171/61042 |
| work_keys_str_mv | AT urdiciainezpeletaaalejandro elpapeldelahistonadesacetilasa6eneldesarrollodelgioblastoma AT saezcastresanajjavier elpapeldelahistonadesacetilasa6eneldesarrollodelgioblastoma |