Delgado-Bellido, DanielFernández-Cortés, MónicaRodríguez, María IsabelSerrano-Sáenz, SantiagoCarracedo, ArkaitzGarcia-Diaz, AngelOliver, F Javier2023-01-252023-01-252018-05-21http://hdl.handle.net/10668/12494Aberrant extra-vascular expression of VE-cadherin (VEC) has been observed in metastasis associated with vasculogenic mimicry (VM); however, the ultimate reason why non-endothelial VEC favors the acquisition of this phenotype is not established. In this study, we show that human malignant melanoma cells have a constitutively high expression of phoshoVEC (pVEC) at Y658; pVEC is a target of focal adhesion kinase (FAK) and forms a complex with p120-catenin and the transcriptional repressor kaiso in the nucleus. FAK inhibition enabled kaiso to suppress the expression of its target genes and enhanced kaiso recruitment to KBS-containing promoters. Finally we have found that ablation of kaiso-repressed genes WNT11 and CCDN1 abolished VM. Thus, identification of pVEC as a component of the kaiso transcriptional complex establishes a molecular paradigm that links FAK-dependent phosphorylation of VEC as a major mechanism by which ectopical VEC expression exerts its function in VM.enAntigens, CDCadherinsCateninsCell Line, TumorCyclin D1Focal Adhesion Kinase 1Gene ExpressionGene Knockout TechniquesHEK293 CellsHuman Umbilical Vein Endothelial CellsHumansMelanomaNeovascularization, PathologicPhosphorylationSkin NeoplasmsTranscription FactorsTransduction, GeneticWnt ProteinsDelta Cateninresearch article29786069open access10.1038/s41418-018-0125-41476-5403PMC6329820https://www.nature.com/articles/s41418-018-0125-4.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329820/pdf