PRL-3/PTP4A3 phosphatase regulates integrin β1 in adhesion structures during migration of human ocular melanoma cells.

摘要: In a previous transcriptomic analysis of 63 ocular melanomas the uvea, we found that expression PRL-3/PTP4A3 gene, encoding phosphatase is anchored to plasma membrane, was associated with risk metastasis, and poor prognosis. We also showed PRL-3 overexpression in OCM-1 melanoma cells significantly increased cell migration vitro invasiveness vivo, suggesting direct role for metastatic spreading uveal melanoma. Here, aimed identify substrates at membrane involved adhesion extracellular matrix. focused on integrin β1, which most highly expressed our cohort melanomas. show preventing anchorage i) abolishes PRL-3-induced cells, ii) specifically enhances overexpressing PRL-3, iii) favors maturation large focal adhesions (FAs) containing β1 collagen I. Knockdown experiments confirmed involvement PRL3-induced migration. identified interactions between as well FAK P-Y397, an auto-activated form Focal Adhesion Kinase FAs. may be dephosphorylated by its intracytoplasmic S/T region, important motif integrin-mediated adhesion. Finally, observed regulated clustering FAs I but not fibronectin. This work identifies new regulator structures matrix, further supports key actor metastasis melanoma, molecular mechanisms are still poorly understood.