VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma.
Luis Francisco Lorenzo-MartínNatalia Fernández-ParejoMauricio Menacho-MárquezSonia Rodríguez-FdezJavier Robles-ValeroSonia ZumalaveSalvatore FabbianoGloria PascualJuana M García-PedreroAntonio AbadMaría Carmen García-MacíasNazareno GonzálezPablo Lorenzano-MennaMiguel A PavónRogelio González-SarmientoCarmen SegrellesJesus M ParamioJosé M C TubíoJuan Pablo RodrigoSalvador Aznar BenitahMyriam CuadradoXosé R BusteloPublished in: Nature communications (2020)
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.
Keyphrases
- poor prognosis
- cell therapy
- stem cells
- genome wide
- mesenchymal stem cells
- signaling pathway
- long non coding rna
- induced apoptosis
- tissue engineering
- public health
- cell cycle arrest
- single cell
- protein kinase
- wound healing
- dna methylation
- transcription factor
- case report
- bone marrow
- gene expression
- pi k akt
- smooth muscle
- immune response
- endoplasmic reticulum stress