Exp Mol Med.
2017 Jul;49(7):e351. 10.1038/emm.2017.88.
Dynamic relocalization of NHERF1 mediates chemotactic migration of ovarian cancer cells toward lysophosphatidic acid stimulation
- Affiliations
-
- 1Department of Brain-Cognitive Science, Daegu-Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea. ysoh2040@dgist.ac.kr
- 2Research Institute, National Cancer Center, Goyang, Republic of Korea.
- 3Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, Republic of Korea. pgsuh@unist.ac.kr
- 4MRC for Ischemic Tissue Regeneration, Department of Pharmacology, School of Medicine, Pusan National University, Yangsan, Republic of Korea.
- 5Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea.
- 6Synaptic Circuit Plasticity Laboratory, Department of Structure and Function of Neural Network, Korea Brain Research Institute, Daegu, Republic of Korea.
- 7School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Institute of Life Science and Biotechnology, Kyungpook National University, Daegu, Republic of Korea.
- 8Division of Molecular and Life Science, Department of Life Science, Pohang University of Science and Technology, Pohang, Republic of Korea.
- KMID: 2388349
- DOI: http://doi.org/10.1038/emm.2017.88
Abstract
- NHERF1/EBP50 (Naâº/H⺠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.
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Lysophosphatidic acid receptor 2 and Gi/Src pathway mediate cell motility through cyclooxygenase 2 expression in CAOV-3 ovarian cancer cells
- Lysophosphatidic acid induces cell migration through the selective activation of Akt1
- Action and Signaling of Lysophosphatidylethanolamine in MDA-MB-231 Breast Cancer Cells
- Facile Titrimetric Assay of Lysophosphatidic Acid in Human Serum and Plasma for Ovarian Cancer Detection
- Kruppel-like factor 4 mediates lysophosphatidic acid-stimulated migration and proliferation of PC3M prostate cancer cells
