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Título: | VE-cadherin promotes vasculogenic mimicry by modulating kaiso-dependent gene expression |
Autor: | Delgado-Bellido, Daniel CSIC ORCID; Fernández-Cortés, Mónica; Rodríguez, María Isabel; Serrano-Sáenz, Santiago CSIC ORCID; Carracedo, Arkaitz CSIC ORCID; García-Díaz, Ángel CSIC ORCID; Oliver, Francisco Javier | Fecha de publicación: | feb-2019 | Editor: | Springer Nature | Citación: | Cell Death and Differentiation | Resumen: | 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. | URI: | http://hdl.handle.net/10261/196006 | DOI: | 10.1038/s41418-018-0125-4 | ISSN: | 1350-9047 | E-ISSN: | 1476-5403 |
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