PRL-3/PTP4A3 phosphatase regulates integrin β1 in adhesion structures during migration of human ocular melanoma cells
| Autor: | Océane Anézo, Malika Foy, Nathalie Planque, Simon Saule |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Uveal Neoplasms endocrine system Integrin CD18 CD49c Collagen receptor Focal adhesion 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor Cell Adhesion Humans Neoplasm Metastasis Cell adhesion Melanoma biology Integrin beta1 Cell Membrane Cell Biology Cell biology Extracellular Matrix Neoplasm Proteins Gene Expression Regulation Neoplastic 030104 developmental biology Integrin alpha M 030220 oncology & carcinogenesis Focal Adhesion Kinase 1 Gene Knockdown Techniques biology.protein Integrin beta 6 Protein Tyrosine Phosphatases hormones hormone substitutes and hormone antagonists |
| Zdroj: | Experimental cell research. 353(2) |
| ISSN: | 1090-2422 |
| Popis: | In a previous transcriptomic analysis of 63 ocular melanomas of the uvea, we found that expression of the PRL-3/PTP4A3 gene, encoding a phosphatase that is anchored to the plasma membrane, was associated with the risk of metastasis, and a poor prognosis. We also showed that PRL-3 overexpression in OCM-1 ocular melanoma cells significantly increased cell migration in vitro and invasiveness in vivo, suggesting a direct role for PRL-3 in the metastatic spreading of uveal melanoma. Here, we aimed to identify PRL-3 substrates at the plasma membrane involved in adhesion to the extracellular matrix. We focused on integrin β1, which is the most highly expressed integrin in our cohort of uveal melanomas. We show that preventing PRL-3 anchorage to the plasma membrane i) abolishes PRL-3-induced migration in OCM-1 cells, ii) specifically enhances the spreading of OCM-1 cells overexpressing PRL-3, and iii) favors the maturation of large focal adhesions (FAs) containing integrin β1 on collagen I. Knockdown experiments confirmed integrin β1 involvement in PRL3-induced migration. We identified interactions between PRL-3 and integrin β1, as well as with FAK P-Y397, an auto-activated form of Focal Adhesion Kinase found in FAs. We also show that integrin β1 may be dephosphorylated by PRL-3 in its intracytoplasmic S/T region, an important motif for integrin-mediated cell adhesion. Finally, we observed that PRL-3 regulated the clustering of integrin β1 in FAs on collagen I but not on fibronectin. This work identifies PRL-3 as a new regulator of cell adhesion structures to the extracellular matrix, and further supports PRL-3 as a key actor of metastasis in uveal melanoma, of which molecular mechanisms are still poorly understood. |
| Databáze: | OpenAIRE |
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