VE-PTP participates in vasculogenic mimicry by preventing autophagic degradation of VE-cadherin [article]

Javier Oliver, Daniel Delgado-Bellido, Angel Garcia-Diaz, Concepcion Bueno-Galera
2019 bioRxiv   pre-print
Aberrant extra-vascular expression of VE-cadherin has been observed in metastasis associated with Vasculogenic Mimicry (VM); we have recently shown that in VM prone (VM+) tumor cells VE-cadherin is mainly in the form of pVE-cadherin in Y658 allowing an increased plasticity that potentiates VM development. As excessive VE-cadherin phosphorylation is regulated by the phosphatase VEPTP in endothelial cells in the current study we analysed its role in this aberrant phenotype in malignant tumor
more » ... alignant tumor cells. We show that human malignant melanoma cells VM+, also express VE-PTP although at lower levels than endothelial cells. The complex VE-PTP/VE-Cadherin/p120-catenin act as a safeguard to prevent VE-cadherin degradation by autophagy. Indeed, silencing of VE-PTP results in complete degradation of VE-cadherin with the features of autophagy and increases the global p120 tyrosine phosphorylation status. In summary, we show that VE-PTP is involved in VM formation and disruption of VE-PTP/VE-Cadherin/p120 complex results in enhanced autophagy in aggressive VM+ cells.
doi:10.1101/634584 fatcat:umfahllvajet7jkknc7zzh4uwy