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

L. Francisco Lorenzo-Martín, Natalia Fernández-Parejo, Mauricio Menacho-Márquez, Sonia Rodríguez-Fdez, Javier Robles-Valero, Sonia Zumalave, Salvatore Fabbiano, Gloria Pascual, Juana M. García-Pedrero, Antonio Abad, María C. García-Macías, Nazareno González, Pablo Lorenzano-Menna, Miguel A. Pavón, Rogelio González-Sarmiento, Carmen Segrelles, Jesús M. Paramio, José M. C. Tubío, Juan P. Rodrigo, Salvador A. Benitah, Myriam Cuadrado and Xosé R. Bustelo ()
Additional contact information
L. Francisco Lorenzo-Martín: Centro de Investigación del Cáncer, CSIC-University of Salamanca
Natalia Fernández-Parejo: Centro de Investigación del Cáncer, CSIC-University of Salamanca
Mauricio Menacho-Márquez: Centro de Investigación del Cáncer, CSIC-University of Salamanca
Sonia Rodríguez-Fdez: Centro de Investigación del Cáncer, CSIC-University of Salamanca
Javier Robles-Valero: Centro de Investigación del Cáncer, CSIC-University of Salamanca
Sonia Zumalave: Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela
Salvatore Fabbiano: Centro de Investigación del Cáncer, CSIC-University of Salamanca
Gloria Pascual: Institute for Research in Biomedicine
Juana M. García-Pedrero: Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca
Antonio Abad: Centro de Investigación del Cáncer, CSIC-University of Salamanca
María C. García-Macías: Centro de Investigación del Cáncer, CSIC-University of Salamanca
Nazareno González: Centro de Investigación del Cáncer, CSIC-University of Salamanca
Pablo Lorenzano-Menna: Laboratory of Molecular Oncology and National University of Quilmes
Miguel A. Pavón: Institut Català d’Oncologia
Rogelio González-Sarmiento: Centro de Investigación del Cáncer, CSIC-University of Salamanca
Carmen Segrelles: Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca
Jesús M. Paramio: Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca
José M. C. Tubío: Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela
Juan P. Rodrigo: Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca
Salvador A. Benitah: Institute for Research in Biomedicine
Myriam Cuadrado: Centro de Investigación del Cáncer, CSIC-University of Salamanca
Xosé R. Bustelo: Centro de Investigación del Cáncer, CSIC-University of Salamanca

Nature Communications, 2020, vol. 11, issue 1, 1-21

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-18524-3

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