Platelet-activating factor regulates cadherin-catenin adhesion system expression and beta-catenin phosphorylation during Kaposi's sarcoma cell motility.
In the present study, we evaluated whether motility of Kaposi's sarcoma (KS) cells induced by platelet-activating factor (PAF) is dependent on the regulation of adherens junctions components. The results obtained indicate that PAF dose and time dependently reduced the endogenous expression of the main components of the adherens junctions: VE-cadherin, alpha-catenin, and beta-catenin. In addition, PAF initiated events that directly or indirectly up-regulated both the tyrosine and serine/threonine phosphorylation pathways, and both types of phosphorylation of beta-catenin were involved in the motility of KS cells. This motility was abrogated by addition of the tyrosine kinase inhibitor genistein, suggesting that this phosphorylation is an important signal responsible for breaking down the adherens junctions and diminishing the ability of neighboring cells to interact. Furthermore, immunofluorescence analysis showed that beta-catenin and VE-cadherin staining changed from a uniform distribution along the membrane of controls to a diffuse pattern with gap formation in PAF-treated KS cells. In conclusion, the data presented here indicate that PAF induces tumor cell motility by altering cell-cell adhesion through beta-catenin phosphorylation.
Boccellino
Mariarosaria
M
Dipartimento di Biochimica e Biofisica, Seconda Università di Napoli, Via Costantinopoli, 16, I-80138 Napoli, Italy.
Camussi
Giovanni
G
Giovane
Alfonso
A
Ferro
Luigi
L
Calderaro
Vincenzo
V
Balestrieri
Ciro
C
Quagliuolo
Lucio
L
D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D010972:Platelet Activating Factor / Q000494:pharmacology*; D012514:Sarcoma, Kaposi / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D014018:Tissue Distribution; D015534:Trans-Activators / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D051178:alpha Catenin; D051176:beta Catenin; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D003598:Cytoskeletal Proteins; D010972:Platelet Activating Factor; D015534:Trans-Activators; D025801:Ubiquitin; D051178:alpha Catenin; D051176:beta Catenin; D000099152:Cadherin 5; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human