Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/261169
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Cancer-associated mutations in VAV1 trigger variegated signaling outputs and T-cell lymphomagenesis |
Autor: | Robles-Valero, Javier CSIC ORCID; Fernández-Nevado, Lucía; Lorenzo-Martín, L. Francisco CSIC ORCID; Cuadrado, Myriam CSIC ORCID; Fernández-Pisonero, Isabel CSIC ORCID; Rodríguez-Fdez, Sonia CSIC ORCID; Astorga-Simón, Elsa N.; Abad, Antonio; Caloto, Rubén; Bustelo, Xosé R. CSIC ORCID | Palabras clave: | Angioimmunoblastic T-cell lymphoma Follicular helper T cells Oncogene Peripheral T-cell lymphoma Tumor suppressor |
Fecha de publicación: | 15-nov-2021 | Editor: | EMBO Press | Citación: | EMBO Journal 40(22): e108125 (2021) | Resumen: | Mutations in VAV1, a gene that encodes a multifunctional protein important for lymphocytes, are found at different frequencies in peripheral T-cell lymphoma (PTCL), non-small cell lung cancer, and other tumors. However, their pathobiological significance remains unsettled. After cataloguing 51 cancer-associated VAV1 mutations, we show here that they can be classified in five subtypes according to functional impact on the three main VAV1 signaling branches, GEF-dependent activation of RAC1, GEF-independent adaptor-like, and tumor suppressor functions. These mutations target new and previously established regulatory layers of the protein, leading to quantitative and qualitative changes in VAV1 signaling output. We also demonstrate that the most frequent VAV1 mutant subtype drives PTCL formation in mice. This process requires the concurrent engagement of two downstream signaling branches that promote the chronic activation and transformation of follicular helper T cells. Collectively, these data reveal the genetic constraints associated with the lymphomagenic potential of VAV1 mutant subsets, similarities with other PTCL driver genes, and potential therapeutic vulnerabilities. | Descripción: | © 2021 The Authors. | Versión del editor: | http://dx.doi.org/10.15252/embj.2021108125 | URI: | http://hdl.handle.net/10261/261169 | DOI: | 10.15252/embj.2021108125 | ISSN: | 0261-4189 | E-ISSN: | 1460-2075 |
Aparece en las colecciones: | (IBMCC) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
Cancer-associated mutations in VAV1_Robles_PV_Art2021.pdf | 5,07 MB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
11
checked on 20-abr-2024
WEB OF SCIENCETM
Citations
8
checked on 28-feb-2024
Page view(s)
43
checked on 26-abr-2024
Download(s)
189
checked on 26-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
Este item está licenciado bajo una Licencia Creative Commons