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

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  • L. Francisco Lorenzo-Martín

    (Centro de Investigación del Cáncer, CSIC-University of Salamanca
    Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca
    Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca)

  • Natalia Fernández-Parejo

    (Centro de Investigación del Cáncer, CSIC-University of Salamanca
    Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca
    Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca)

  • Mauricio Menacho-Márquez

    (Centro de Investigación del Cáncer, CSIC-University of Salamanca
    Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca
    Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca
    Instituto de Inmunología Clínica y Experimental de Rosario (IDICER, CONICET-UNR). Facultad de Ciencias Médicas Universidad Nacional de Rosario (M.M.-M.) and CellPress editorial office (S.F.))

  • Sonia Rodríguez-Fdez

    (Centro de Investigación del Cáncer, CSIC-University of Salamanca
    Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca
    Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca)

  • Javier Robles-Valero

    (Centro de Investigación del Cáncer, CSIC-University of Salamanca
    Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca
    Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 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
    Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca
    Instituto de Inmunología Clínica y Experimental de Rosario (IDICER, CONICET-UNR). Facultad de Ciencias Médicas Universidad Nacional de Rosario (M.M.-M.) and CellPress editorial office (S.F.))

  • Gloria Pascual

    (Institute for Research in Biomedicine
    The Barcelona Institute of Science and Technology)

  • Juana M. García-Pedrero

    (Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca
    Hospital Universitario Central de Asturias, Oviedo University)

  • Antonio Abad

    (Centro de Investigación del Cáncer, CSIC-University of Salamanca
    Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca
    Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca)

  • María C. García-Macías

    (Centro de Investigación del Cáncer, CSIC-University of Salamanca
    Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca
    Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca)

  • Nazareno González

    (Centro de Investigación del Cáncer, CSIC-University of Salamanca
    Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca)

  • Pablo Lorenzano-Menna

    (Laboratory of Molecular Oncology and National University of Quilmes
    National Council of Scientific and Technical Research (CONICET), National University of Quilmes)

  • Miguel A. Pavón

    (Institut Català d’Oncologia
    Centro Biomédica de Investigación en Red de Enfermedades Respiratorias (CIBERESP))

  • Rogelio González-Sarmiento

    (Centro de Investigación del Cáncer, CSIC-University of Salamanca
    Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca
    Instituto de Investigación Biomédica de Salamanca)

  • Carmen Segrelles

    (Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca
    Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas)

  • Jesús M. Paramio

    (Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca
    Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas)

  • 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
    Hospital Universitario Central de Asturias, Oviedo University)

  • Salvador A. Benitah

    (Institute for Research in Biomedicine
    The Barcelona Institute of Science and Technology
    Catalan Institution for Research and Advanced Studies (ICREA))

  • Myriam Cuadrado

    (Centro de Investigación del Cáncer, CSIC-University of Salamanca
    Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca
    Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca)

  • Xosé R. Bustelo

    (Centro de Investigación del Cáncer, CSIC-University of Salamanca
    Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca
    Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca)

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.

Suggested Citation

  • 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, 2020. "VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma," Nature Communications, Nature, vol. 11(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18524-3
    DOI: 10.1038/s41467-020-18524-3
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    Cited by:

    1. Olga Boix & Marion Martinez & Santiago Vidal & Marta Giménez-Alejandre & Lluís Palenzuela & Laura Lorenzo-Sanz & Laura Quevedo & Olivier Moscoso & Jorge Ruiz-Orera & Pilar Ximénez-Embún & Nikaoly Ciri, 2022. "pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation," Nature Communications, Nature, vol. 13(1), pages 1-22, December.

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