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

Lorenzo Martín, L. Francisco; Fernández Parejo, Natalia; Menacho Márquez, Mauricio; Rodríguez-Fdez, Sonia; Robles Valero, Javier; Zumalave, Sonia; Fabbiano, Salvatore; Pascual, Gloria; Garcia Pedrero, Juana M.; Abad, Antonio; García Macías, María C.; González, Nazareno; Lorenzano Menna, Pablo; Pavón Ribas, Miquel Àngel; González Sarmiento, Rogelio; Segrelles, Carmen; Paramio, Jesús M.; Tubío, José M. C.; Rodrigo, Juan P.; Benitah, Salvador A.; Cuadrado, Myriam; Bustelo, Xosé R.

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

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 GTP...

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Autores:	Lorenzo Martín, L. Francisco, Fernández Parejo, Natalia, Menacho Márquez, Mauricio, Rodríguez-Fdez, Sonia, Robles Valero, Javier, Zumalave, Sonia, Fabbiano, Salvatore, Pascual, Gloria, Garcia Pedrero, Juana M., Abad, Antonio, García Macías, María C., González, Nazareno, Lorenzano Menna, Pablo, Pavón Ribas, Miquel Àngel, 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:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:2445/174077
Acceso en línea:	https://hdl.handle.net/2445/174077
Access Level:	acceso abierto
Palabra clave:	Càncer de cap Càncer de coll Pronòstic mèdic Head cancer Neck cancer Prognosis

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spelling	VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinomaLorenzo Martín, L. FranciscoFernández Parejo, NataliaMenacho Márquez, MauricioRodríguez-Fdez, SoniaRobles Valero, JavierZumalave, SoniaFabbiano, SalvatorePascual, GloriaGarcia Pedrero, Juana M.Abad, AntonioGarcía Macías, María C.González, NazarenoLorenzano Menna, PabloPavón Ribas, Miquel ÀngelGonzález Sarmiento, RogelioSegrelles, CarmenParamio, Jesús M.Tubío, José M. C.Rodrigo, Juan P.Benitah, Salvador A.Cuadrado, MyriamBustelo, Xosé R.Càncer de capCàncer de collPronòstic mèdicHead cancerNeck cancerPrognosisRegenerative 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. The Rho signalling pathway is frequently activated in squamous carcinomas. Here, the authors find that the Rho GEF VAV2 is over expressed in both cutaneous and head and neck squamous cell carcinomas and that at the molecular level VAV2 promotes a pro-tumorigenic stem cell-like signalling programme.Nature Research2021202120202021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion21 p.application/pdfhttps://hdl.handle.net/2445/174077Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1038/s41467-020-18524-3Nature Communications, 2020 vol. 11https://doi.org/10.1038/s41467-020-18524-3cc by (c) Lorenzo Martín et al., 2020http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1740772026-05-29T05:05:01Z
dc.title.none.fl_str_mv	VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma
title	VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma
spellingShingle	VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma Lorenzo Martín, L. Francisco Càncer de cap Càncer de coll Pronòstic mèdic Head cancer Neck cancer Prognosis
title_short	VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma
title_full	VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma
title_fullStr	VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma
title_full_unstemmed	VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma
title_sort	VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma
dc.creator.none.fl_str_mv	Lorenzo Martín, L. Francisco Fernández Parejo, Natalia Menacho Márquez, Mauricio Rodríguez-Fdez, Sonia Robles Valero, Javier Zumalave, Sonia Fabbiano, Salvatore Pascual, Gloria Garcia Pedrero, Juana M. Abad, Antonio García Macías, María C. González, Nazareno Lorenzano Menna, Pablo Pavón Ribas, Miquel Àngel González Sarmiento, Rogelio Segrelles, Carmen Paramio, Jesús M. Tubío, José M. C. Rodrigo, Juan P. Benitah, Salvador A. Cuadrado, Myriam Bustelo, Xosé R.
author	Lorenzo Martín, L. Francisco
author_facet	Lorenzo Martín, L. Francisco Fernández Parejo, Natalia Menacho Márquez, Mauricio Rodríguez-Fdez, Sonia Robles Valero, Javier Zumalave, Sonia Fabbiano, Salvatore Pascual, Gloria Garcia Pedrero, Juana M. Abad, Antonio García Macías, María C. González, Nazareno Lorenzano Menna, Pablo Pavón Ribas, Miquel Àngel González Sarmiento, Rogelio Segrelles, Carmen Paramio, Jesús M. Tubío, José M. C. Rodrigo, Juan P. Benitah, Salvador A. Cuadrado, Myriam Bustelo, Xosé R.
author_role	author
author2	Fernández Parejo, Natalia Menacho Márquez, Mauricio Rodríguez-Fdez, Sonia Robles Valero, Javier Zumalave, Sonia Fabbiano, Salvatore Pascual, Gloria Garcia Pedrero, Juana M. Abad, Antonio García Macías, María C. González, Nazareno Lorenzano Menna, Pablo Pavón Ribas, Miquel Àngel González Sarmiento, Rogelio Segrelles, Carmen Paramio, Jesús M. Tubío, José M. C. Rodrigo, Juan P. Benitah, Salvador A. Cuadrado, Myriam Bustelo, Xosé R.
author2_role	author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Càncer de cap Càncer de coll Pronòstic mèdic Head cancer Neck cancer Prognosis
topic	Càncer de cap Càncer de coll Pronòstic mèdic Head cancer Neck cancer Prognosis
description	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. The Rho signalling pathway is frequently activated in squamous carcinomas. Here, the authors find that the Rho GEF VAV2 is over expressed in both cutaneous and head and neck squamous cell carcinomas and that at the molecular level VAV2 promotes a pro-tumorigenic stem cell-like signalling programme.
publishDate	2020
dc.date.none.fl_str_mv	2020 2021 2021 2021
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/174077
url	https://hdl.handle.net/2445/174077
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: https://doi.org/10.1038/s41467-020-18524-3 Nature Communications, 2020 vol. 11 https://doi.org/10.1038/s41467-020-18524-3
dc.rights.none.fl_str_mv	cc by (c) Lorenzo Martín et al., 2020 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc by (c) Lorenzo Martín et al., 2020 http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	21 p. application/pdf
dc.publisher.none.fl_str_mv	Nature Research
publisher.none.fl_str_mv	Nature Research
dc.source.none.fl_str_mv	Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma

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