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Dynamic relocalization of NHERF1 mediates chemotactic migration of ovarian cancer cells toward lysophosphatidic acid stimulation
- Dynamic relocalization of NHERF1 mediates chemotactic migration of ovarian cancer cells toward lysophosphatidic acid stimulation
- Oh, Y.-S.; Heo, K.; Kim, E.-K.; Jang, J.-H.; Bae, S.S.; Park, J.B.; Kim, Y.H.; Song, M.; Kim, S.R.; Ryu, S.H.; Kim, I.-H.; Suh, P.-G.
- DGIST Authors
- Oh, Y.-S.; Jang, J.-H.
- Issue Date
- Experimental and Molecular Medicine, 49(7)
- Article Type
- 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. © 2017 KSBMB. All rights reserved.
- Nature Publishing Group
- Related Researcher
Laboratory of Neural Signaling Networks
Monoaminergic regulation of the CNS and mood;anxiety disorder; 모노아민 (세로토닌, 도파민)에 의한 신경조절과 기분;불안 장애 기전 연구
- Department of Brain and Cognitive SciencesLaboratory of Neural Signaling Networks1. Journal Articles
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