Dynamic relocalization of NHERF1 mediates chemotactic migration of ovarian cancer cells toward lysophosphatidic acid stimulation
| Autor: | Sang Ryong Kim, Eung-Kyun Kim, Yong-Seok Oh, Sung Ho Ryu, Jong Bae Park, Minseok Song, Jin-Hyeok Jang, Sun Sik Bae, Kyun Heo, Pann-Ghill Suh, In-Hoo Kim, Yun-Hee Kim |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cytoplasm Sodium-Hydrogen Exchangers Clinical Biochemistry Down-Regulation Biology Biochemistry Cell membrane 03 medical and health sciences chemistry.chemical_compound Cell Line Tumor Cell cortex Lysophosphatidic acid medicine Humans Pseudopodia Molecular Biology Ovarian Neoplasms Chemotaxis Cell Membrane Cell migration Apical membrane Phosphoproteins Cell biology Cytoskeletal Proteins Protein Transport 030104 developmental biology medicine.anatomical_structure chemistry Cancer cell Mutation Disease Progression Molecular Medicine Female Original Article Lysophospholipids Protein Binding |
| Zdroj: | Experimental & Molecular Medicine |
| ISSN: | 2092-6413 |
| Popis: | NHERF1/EBP50 (Na+/H+ exchanger regulating factor 1; Ezrin-binding phosphoprotein of 50 kDa) organizes stable protein complexes beneath the apical membrane of polar epithelial cells. By contrast, in cancer cells without any fixed polarity, NHERF1 often localizes in the cytoplasm. The regulation of cytoplasmic NHERF1 and its role in cancer progression remain unclear. In this study, we found that, upon lysophosphatidic acid (LPA) stimulation, cytoplasmic NHERF1 rapidly translocated to the plasma membrane, and subsequently to cortical protrusion structures, of ovarian cancer cells. This movement depended on direct binding of NHERF1 to C-terminally phosphorylated ERM proteins (cpERMs). Moreover, NHERF1 depletion downregulated cpERMs and further impaired cpERM-dependent remodeling of the cell cortex, suggesting reciprocal regulation between these proteins. The LPA-induced protein complex was highly enriched in migratory pseudopodia, whose formation was impaired by overexpression of NHERF1 truncation mutants. Consistent with this, NHERF1 depletion in various types of cancer cells abolished chemotactic cell migration toward a LPA gradient. Taken together, our findings suggest that the high dynamics of cytosolic NHERF1 provide cancer cells with a means of controlling chemotactic migration. This capacity is likely to be essential for ovarian cancer progression in tumor microenvironments containing LPA. |
| Databáze: | OpenAIRE |
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