Phosphorylation and disorganization of vascular-endothelial cadherin in interaction between breast cancer and vascular endothelial cells.
Adherens junctions of the endothelium play a key role in the maintenance of endothelial permeability and are composed of the vascular endothelial (VE)-cadherin/catenin adhesion complex. We report that following tumour cell (MDA MB231 cells) adherence to the HUVECs, there was a rapid (within 5 min) redistribution of VE-cadherin, resulting in its transient loss from regions of endothelial cell-cell contact. The molecule gradually reorganised within the endothelial cell contacts after this time. It was further shown that the overall expression of VE-cadherin did not change, however, the amount of alpha- and beta-catenins coprecipitated with VE-cadherin markedly decreased after 5 min of tumour cell adhesion to the HUVECs. Immunoprobing of these samples with anti-phosphotyrosine antibodies demonstrated that the tyrosine phosphorylation of VE-cadherin was significantly increased following 5 min of tumour cell adhesion. Together, these results suggest that the adhesion of tumour cells to HUVEC promotes the redistribution of VE-cadherin from interendothelial adherens junctions, an effect that may be attributed to the increase in tyrosine phosphorylation of members of the VE-cadherin/catenin adhesion complex. This, in turn, may increase vascular endothelial permeability and facilitate the transendothelial migration of tumour cells during extravasation.
Cai
J
J
Metastasis Research Group, University Department of Surgery, University of Wales College of Medicine, Cardiff CF4 4XN, UK.
Jiang
W G
WG
Mansel
R E
RE
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D018920:Coculture Techniques; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051178:alpha Catenin; D051176:beta Catenin
C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin