Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/222386
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Transcription factor NRF2 uses the Hippo pathway effector TAZ to induce tumorigenesis in glioblastomas |
Autor: | Escoll, Maribel CSIC ORCID; Lastra, Diego CSIC; Pajares, Marta CSIC; Robledinos-Antón, Natalia CSIC; Rojo, Ana I. CSIC ORCID; Fernández-Ginés, Raquel CSIC; Mendiola, Marta; Martínez-Marín, Virginia; Esteban Rodriguez, Isabel; López-Larrubia, Pilar CSIC ORCID; Gargini, Ricardo CSIC ORCID; Cuadrado, Antonio CSIC ORCID | Palabras clave: | Oxidative stress Glioblastoma Cancer stem cells Chemotherapy |
Fecha de publicación: | 2020 | Editor: | Elsevier | Citación: | Redox Biology 30: 101425 (2020) | Resumen: | Transcription factor NRF2 orchestrates a cellular defense against oxidative stress and, so far, has been involved in tumor progression by providing a metabolic adaptation to tumorigenic demands and resistance to chemotherapeutics. In this study, we discover that NRF2 also propels tumorigenesis in gliomas and glioblastomas by inducing the expression of the transcriptional co-activator TAZ, a protein of the Hippo signaling pathway that promotes tumor growth. The expression of the genes encoding NRF2 (NFE2L2) and TAZ (WWTR1) showed a positive correlation in 721 gliomas from The Cancer Genome Atlas database. Moreover, NRF2 and TAZ protein levels also correlated in immunohistochemical tissue arrays of glioblastomas. Genetic knock-down of NRF2 decreased, while NRF2 overexpression or chemical activation with sulforaphane, increased TAZ transcript and protein levels. Mechanistically, we identified several NRF2-regulated functional enhancers in the regulatory region of WWTR1. The relevance of the new NRF2/TAZ axis in tumorigenesis was demonstrated in subcutaneous and intracranial grafts. Thus, intracranial inoculation of NRF2-depleted glioma stem cells did not develop tumors as determined by magnetic resonance imaging. Forced TAZ overexpression partly rescued both stem cell growth in neurospheres and tumorigenicity. Hence, NRF2 not only enables tumor cells to be competent to proliferate but it also propels tumorigenesis by activating the TAZ-mediated Hippo transcriptional program. | Versión del editor: | https://doi.org/10.1016/j.redox.2019.101425 | URI: | http://hdl.handle.net/10261/222386 | DOI: | 10.1016/j.redox.2019.101425 | E-ISSN: | 2213-2317 |
Aparece en las colecciones: | (IIBM) Artículos (CBM) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
transcrigliobla.pdf | 3,05 MB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
PubMed Central
Citations
19
checked on 10-mar-2024
SCOPUSTM
Citations
25
checked on 15-abr-2024
WEB OF SCIENCETM
Citations
23
checked on 22-feb-2024
Page view(s)
191
checked on 18-abr-2024
Download(s)
183
checked on 18-abr-2024