VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma
Authors
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, Xosé R. Bustelo
Institution
University of Salamanca
Country
Spain
Year
2020
Journal
Nature Communications
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.
Product use
Keratinocyte isolation and culture, 3D epidermal models