VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma
Menée notamment à l'aide de modèles murins et d'échantillons tumoraux, cette étude met en évidence un mécanisme par lequel la signalisation de la protéine VAV2 favorise le renouvellement et la prolifération des cellules des carcinomes épidermoïdes cutanés et des carcinomes épidermoïdes de la tête et du cou
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.