VE-cadherin Promotes Vasculogenic Mimicry by Modulating Kaiso-dependent Gene Expression

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2018 May 23

PMID 29786069

Citations 32

Authors

Daniel Delgado-Bellido

Monica Fernandez-Cortes

Maria Isabel Rodriguez

Santiago Serrano-Saenz

Arkaitz Carracedo

Angel Garcia-Diaz

F Javier Oliver

Affiliations

Soon will be listed here.

Abstract

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.

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