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Early Events in Actin Cytoskeleton Dynamics and E-Cadherin-Mediated Cell-Cell Adhesion during Epithelial-Mesenchymal Transition

Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, 115478 Moscow, Russia
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Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(3), 578; https://doi.org/10.3390/cells9030578
Received: 22 February 2020 / Accepted: 28 February 2020 / Published: 29 February 2020
(This article belongs to the Section Cell Motility and Adhesion)
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. View Full-Text
Keywords: epithelial-mesenchymal transition; actin cytoskeleton; cell-cell adhesion; E-cadherin; EPLIN epithelial-mesenchymal transition; actin cytoskeleton; cell-cell adhesion; E-cadherin; EPLIN
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Zhitnyak, I.Y.; Rubtsova, S.N.; Litovka, N.I.; Gloushankova, N.A. Early Events in Actin Cytoskeleton Dynamics and E-Cadherin-Mediated Cell-Cell Adhesion during Epithelial-Mesenchymal Transition. Cells 2020, 9, 578.

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