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Title: VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma
Author: 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.
Keywords: Càncer de cap
Càncer de coll
Pronòstic mèdic
Head cancer
Neck cancer
Issue Date: 22-Sep-2020
Publisher: Nature Research
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: Nature Communications, 2020 vol. 11
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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