VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma.

[EN]Regenerative proliferation capacity and poor differentiation are histological features usually linked to poor prognosis in head and neck squamous cell carcinoma (hnSCC). However, the pathways that regulate them remain ill-characterized. Here, we show that those traits can be triggered by the RHO...

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Detalles Bibliográficos
Autores: Lorenzo Martín, Luis Francisco, Fernández-Parejo, Natalia, Menacho-Márquez, Mauricio, Rodríguez-Fdez, Sonia, Robles-Valero, Javier, Zumalave, Sonia, Fabbiano, Salvatore, Pascual, Gloria, García-Pedrero, Juana M, Abad, Antonio, García Macias, María del Carmen, González, Nazareno, Lorenzano-Menna, Pablo, Pavón, Miguel A, González Sarmiento, Rogelio, Segrelles, Carmen, Paramio, Jesús M, Tubío, José M C, Rodrigo, Juan P, Benitah, Salvador A, Cuadrado, Myriam, Bustelo, Xosé R.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/166938
Acceso en línea:http://hdl.handle.net/10366/166938
Access Level:acceso abierto
Palabra clave:Head and neck squamous cell carcinoma
RHO GTPase
RHO guanosine nucleotide exchange factors
Keratinocytes
Proto-Oncogene Proteins c-vav
Transcriptome
Epidermis
Cell Differentiation
Gene Expression Regulation
Signal Transduction
Gene Knockdown Techniques
Head and Neck Neoplasms
Cell Proliferation
Mice
3207.13 Oncología
queratinocitos
diferenciación celular
regulación de la expresión génica
transducción de señales
ratones
proteínas protooncogénicas c-vav
técnicas de silenciamiento génico
transcriptoma
epidermis
proliferación celular
neoplasias de cabeza y cuello
Descripción
Sumario:[EN]Regenerative proliferation capacity and poor differentiation are histological features usually linked to poor prognosis in head and neck squamous cell carcinoma (hnSCC). However, the pathways that regulate them remain ill-characterized. Here, we show that those traits can be triggered by the RHO GTPase activator VAV2 in keratinocytes present in the skin and oral mucosa. VAV2 is also required to maintain those traits in hnSCC patient-derived cells. This function, which is both catalysis- and RHO GTPase-dependent, is mediated by c-Myc- and YAP/TAZ-dependent transcriptomal programs associated with regenerative proliferation and cell undifferentiation, respectively. High levels of VAV2 transcripts and VAV2-regulated gene signatures are both associated with poor hnSCC patient prognosis. These results unveil a druggable pathway linked to the malignancy of specific SCC subtypes.

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