Protein Tyrosine Phosphatase 4A3 (PTP4A3) Promotes Human Uveal Melanoma Aggressiveness Through Membrane Accumulation of Matrix Metalloproteinase 14 (MMP14)
| Autor: | Nathalie Cassoux, Océane Anezo, Nathalie Planque, Cécile Laurent, S Saule, Sophie Piperno-Neumann, Selma Maacha, Malika Foy, Laurence Mery, Xavier Sastre-Garau, Géraldine Liot |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Uveal Neoplasms Phosphatase Cell Uveal Neoplasm Fluorescent Antibody Technique Protein tyrosine phosphatase Biology Cell membrane 03 medical and health sciences Cell Movement Cell Line Tumor medicine Matrix Metalloproteinase 14 Humans Neoplasm Invasiveness Neoplasm Metastasis Uvea Melanoma Cell Membrane Cell migration Flow Cytometry Neoplasm Proteins 030104 developmental biology medicine.anatomical_structure Cell culture Cancer research RNA Interference Protein Tyrosine Phosphatases |
| Zdroj: | Investigative ophthalmologyvisual science. 57(4) |
| ISSN: | 1552-5783 |
| Popis: | PURPOSE To study PTP4A3 phosphatase and MMP14 metalloprotease synergy in uveal melanoma aggressiveness. METHODS Cell membrane localization of matrix metalloprotease 14 (MMP14) in uveal melanoma cells expressing protein tyrosine phosphatase A3 (PTP4A3) was assessed by flow cytometry or immunohistochemistry. The vesicular trafficking of MMP14 in the presence of PTP4A3 was evaluated in OCM-1 cells expressing either the wild-type or mutated phosphatase. Finally, MMP14 localization at the cell membrane of OCM-1 cells was impaired using RNA interference, and the PTP4A3-related migration in vitro and invasiveness in vivo of the treated cells were evaluated. RESULTS We found that the membrane-anchored MMP14 is enriched at the cell surface of OCM-1 cells, patient-derived xenograft cells, and human primary uveal melanoma tumors expressing PTP4A3. Moreover, we show that PTP4A3 and MMP14 colocalize and that the vesicular trafficking of MMP14 is faster in the presence of active PTP4A3. Finally, we demonstrate that inhibition of MMP14 expression in uveal melanoma cells expressing PTP4A3 impairs their migration in vitro and invasiveness in vivo. CONCLUSIONS Our observations indicate that PTP4A3 increases cell membrane accumulation of MMP14 as a result of increased cellular trafficking of the metalloprotease. We also show that downregulation of MMP14 expression reduced PTP4A3-induced cell migration and invasiveness. Taken together, our findings suggest that PTP4A3-related subcellular localization of MMP14 is an important event in metastasis induction. |
| Databáze: | OpenAIRE |
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