Early Events in Actin Cytoskeleton Dynamics and E-Cadherin-Mediated Cell-Cell Adhesion during Epithelial-Mesenchymal Transition
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 staini...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/3/578 |
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| author | Irina Y. Zhitnyak Svetlana N. Rubtsova Nikita I. Litovka Natalya A. Gloushankova |
| author_facet | Irina Y. Zhitnyak Svetlana N. Rubtsova Nikita I. Litovka Natalya A. Gloushankova |
| author_sort | Irina Y. Zhitnyak |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T06:03:15Z |
| format | Article |
| id | doaj.art-e1dcbe325cc144a59566a340211b04c2 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T06:03:15Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-e1dcbe325cc144a59566a340211b04c22023-09-03T03:59:33ZengMDPI AGCells2073-44092020-02-019357810.3390/cells9030578cells9030578Early Events in Actin Cytoskeleton Dynamics and E-Cadherin-Mediated Cell-Cell Adhesion during Epithelial-Mesenchymal TransitionIrina Y. Zhitnyak0Svetlana N. Rubtsova1Nikita I. Litovka2Natalya A. Gloushankova3These authors contributed equally to this work.These authors contributed equally to this work.Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, 115478 Moscow, RussiaInstitute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, 115478 Moscow, RussiaEpithelial-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.https://www.mdpi.com/2073-4409/9/3/578epithelial-mesenchymal transitionactin cytoskeletoncell-cell adhesione-cadherineplin |
| spellingShingle | Irina Y. Zhitnyak Svetlana N. Rubtsova Nikita I. Litovka Natalya A. Gloushankova Early Events in Actin Cytoskeleton Dynamics and E-Cadherin-Mediated Cell-Cell Adhesion during Epithelial-Mesenchymal Transition Cells epithelial-mesenchymal transition actin cytoskeleton cell-cell adhesion e-cadherin eplin |
| title | Early Events in Actin Cytoskeleton Dynamics and E-Cadherin-Mediated Cell-Cell Adhesion during Epithelial-Mesenchymal Transition |
| title_full | Early Events in Actin Cytoskeleton Dynamics and E-Cadherin-Mediated Cell-Cell Adhesion during Epithelial-Mesenchymal Transition |
| title_fullStr | Early Events in Actin Cytoskeleton Dynamics and E-Cadherin-Mediated Cell-Cell Adhesion during Epithelial-Mesenchymal Transition |
| title_full_unstemmed | Early Events in Actin Cytoskeleton Dynamics and E-Cadherin-Mediated Cell-Cell Adhesion during Epithelial-Mesenchymal Transition |
| title_short | Early Events in Actin Cytoskeleton Dynamics and E-Cadherin-Mediated Cell-Cell Adhesion during Epithelial-Mesenchymal Transition |
| title_sort | early events in actin cytoskeleton dynamics and e cadherin mediated cell cell adhesion during epithelial mesenchymal transition |
| topic | epithelial-mesenchymal transition actin cytoskeleton cell-cell adhesion e-cadherin eplin |
| url | https://www.mdpi.com/2073-4409/9/3/578 |
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