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Vinculin regulates directionality and cell polarity in two- and three-dimensional matrix and three-dimensional microtrack migration
During metastasis, cells can use proteolytic activity to form tube-like “microtracks” within the extracellular matrix (ECM). Using these microtracks, cells can migrate unimpeded through the stroma. To investigate the molecular mechanisms of microtrack migration, we developed an in vitro three-dimens...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850031/ https://www.ncbi.nlm.nih.gov/pubmed/26960796 http://dx.doi.org/10.1091/mbc.E15-06-0432 |
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author | Rahman, Aniqua Carey, Shawn P. Kraning-Rush, Casey M. Goldblatt, Zachary E. Bordeleau, Francois Lampi, Marsha C. Lin, Deanna Y. García, Andrés J. Reinhart-King, Cynthia A. |
author_facet | Rahman, Aniqua Carey, Shawn P. Kraning-Rush, Casey M. Goldblatt, Zachary E. Bordeleau, Francois Lampi, Marsha C. Lin, Deanna Y. García, Andrés J. Reinhart-King, Cynthia A. |
author_sort | Rahman, Aniqua |
collection | PubMed |
description | During metastasis, cells can use proteolytic activity to form tube-like “microtracks” within the extracellular matrix (ECM). Using these microtracks, cells can migrate unimpeded through the stroma. To investigate the molecular mechanisms of microtrack migration, we developed an in vitro three-dimensional (3D) micromolded collagen platform. When in microtracks, cells tend to migrate unidirectionally. Because focal adhesions are the primary mechanism by which cells interact with the ECM, we examined the roles of several focal adhesion molecules in driving unidirectional motion. Vinculin knockdown results in the repeated reversal of migration direction compared with control cells. Tracking the position of the Golgi centroid relative to the position of the nucleus centroid reveals that vinculin knockdown disrupts cell polarity in microtracks. Vinculin also directs migration on two-dimensional (2D) substrates and in 3D uniform collagen matrices, as indicated by reduced speed, shorter net displacement, and decreased directionality in vinculin-deficient cells. In addition, vinculin is necessary for focal adhesion kinase (FAK) activation in three dimensions, as vinculin knockdown results in reduced FAK activation in both 3D uniform collagen matrices and microtracks but not on 2D substrates, and, accordingly, FAK inhibition halts cell migration in 3D microtracks. Together these data indicate that vinculin plays a key role in polarization during migration. |
format | Online Article Text |
id | pubmed-4850031 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-48500312016-07-16 Vinculin regulates directionality and cell polarity in two- and three-dimensional matrix and three-dimensional microtrack migration Rahman, Aniqua Carey, Shawn P. Kraning-Rush, Casey M. Goldblatt, Zachary E. Bordeleau, Francois Lampi, Marsha C. Lin, Deanna Y. García, Andrés J. Reinhart-King, Cynthia A. Mol Biol Cell Articles During metastasis, cells can use proteolytic activity to form tube-like “microtracks” within the extracellular matrix (ECM). Using these microtracks, cells can migrate unimpeded through the stroma. To investigate the molecular mechanisms of microtrack migration, we developed an in vitro three-dimensional (3D) micromolded collagen platform. When in microtracks, cells tend to migrate unidirectionally. Because focal adhesions are the primary mechanism by which cells interact with the ECM, we examined the roles of several focal adhesion molecules in driving unidirectional motion. Vinculin knockdown results in the repeated reversal of migration direction compared with control cells. Tracking the position of the Golgi centroid relative to the position of the nucleus centroid reveals that vinculin knockdown disrupts cell polarity in microtracks. Vinculin also directs migration on two-dimensional (2D) substrates and in 3D uniform collagen matrices, as indicated by reduced speed, shorter net displacement, and decreased directionality in vinculin-deficient cells. In addition, vinculin is necessary for focal adhesion kinase (FAK) activation in three dimensions, as vinculin knockdown results in reduced FAK activation in both 3D uniform collagen matrices and microtracks but not on 2D substrates, and, accordingly, FAK inhibition halts cell migration in 3D microtracks. Together these data indicate that vinculin plays a key role in polarization during migration. The American Society for Cell Biology 2016-05-01 /pmc/articles/PMC4850031/ /pubmed/26960796 http://dx.doi.org/10.1091/mbc.E15-06-0432 Text en © 2016 Rahman et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Rahman, Aniqua Carey, Shawn P. Kraning-Rush, Casey M. Goldblatt, Zachary E. Bordeleau, Francois Lampi, Marsha C. Lin, Deanna Y. García, Andrés J. Reinhart-King, Cynthia A. Vinculin regulates directionality and cell polarity in two- and three-dimensional matrix and three-dimensional microtrack migration |
title | Vinculin regulates directionality and cell polarity in two- and three-dimensional matrix and three-dimensional microtrack migration |
title_full | Vinculin regulates directionality and cell polarity in two- and three-dimensional matrix and three-dimensional microtrack migration |
title_fullStr | Vinculin regulates directionality and cell polarity in two- and three-dimensional matrix and three-dimensional microtrack migration |
title_full_unstemmed | Vinculin regulates directionality and cell polarity in two- and three-dimensional matrix and three-dimensional microtrack migration |
title_short | Vinculin regulates directionality and cell polarity in two- and three-dimensional matrix and three-dimensional microtrack migration |
title_sort | vinculin regulates directionality and cell polarity in two- and three-dimensional matrix and three-dimensional microtrack migration |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850031/ https://www.ncbi.nlm.nih.gov/pubmed/26960796 http://dx.doi.org/10.1091/mbc.E15-06-0432 |
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