期刊
CELLS
卷 9, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/cells9030578
关键词
epithelial-mesenchymal transition; actin cytoskeleton; cell-cell adhesion; E-cadherin; EPLIN
类别
资金
- Russian Science Foundation [16-15-10288]
- Russian Foundation for Basic Research [18-54-16005]
- Russian Science Foundation [19-15-13020] Funding Source: Russian Science Foundation
Epithelial-mesenchymal transition (EMT) plays an important role in development and also in initiation of metastasis during cancer. Disruption of cell-cell contacts during EMT allowing cells to detach from and migrate away from their neighbors remains poorly understood. Using immunofluorescent staining and live-cell imaging, we analyzed early events during EMT induced by epidermal growth factor (EGF) in IAR-20 normal epithelial cells. Control cells demonstrated stable adherens junctions (AJs) and robust contact paralysis, whereas addition of EGF caused rapid dynamic changes at the cell-cell boundaries: fragmentation of the circumferential actin bundle, assembly of actin network in lamellipodia, and retrograde flow. Simultaneously, an actin-binding protein EPLIN was phosphorylated, which may have decreased the stability of the circumferential actin bundle. Addition of EGF caused gradual replacement of linear E-cadherin-based AJs with dynamic and unstable punctate AJs, which, unlike linear AJs, colocalized with the mechanosensitive protein zyxin, confirming generation of centripetal force at the sites of cell-cell contacts during EMT. Our data show that early EMT promotes heightened dynamics at the cell-cell boundaries-replacement of stable AJs and actin structures with dynamic ones-which results in overall weakening of cell-cell adhesion, thus priming the cells for front-rear polarization and eventual migration.
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