%0 Journal Article
%A Delgado-Bellido, Daniel
%A Fernández-Cortés, Mónica
%A Rodríguez, María Isabel
%A Serrano-Sáenz, Santiago
%A Carracedo, Arkaitz
%A Garcia-Diaz, Angel
%A Oliver, F Javier
%T VE-cadherin promotes vasculogenic mimicry by modulating kaiso-dependent gene expression.
%D 2018
%U http://hdl.handle.net/10668/12494
%X Aberrant 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.
%~