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

First Author  Lorenzo-Martín LF Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  4788
PubMed ID  32963234 Mgi Jnum  J:298629
Mgi Id  MGI:6470289 Doi  10.1038/s41467-020-18524-3
Citation  Lorenzo-Martin LF, et al. (2020) VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma. Nat Commun 11(1):4788
abstractText  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.
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