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Cell cycle–dependent force transmission in cancer cells
The generation of traction forces and their transmission to the extracellular environment supports the disseminative migration of cells from a primary tumor. In cancer cells, the periodic variation of nuclear stiffness during the cell cycle provides a functional link between efficient translocation...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254576/ https://www.ncbi.nlm.nih.gov/pubmed/30113874 http://dx.doi.org/10.1091/mbc.E17-12-0726 |
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author | Panagiotakopoulou, Magdalini Lendenmann, Tobias Pramotton, Francesca Michela Giampietro, Costanza Stefopoulos, Georgios Poulikakos, Dimos Ferrari, Aldo |
author_facet | Panagiotakopoulou, Magdalini Lendenmann, Tobias Pramotton, Francesca Michela Giampietro, Costanza Stefopoulos, Georgios Poulikakos, Dimos Ferrari, Aldo |
author_sort | Panagiotakopoulou, Magdalini |
collection | PubMed |
description | The generation of traction forces and their transmission to the extracellular environment supports the disseminative migration of cells from a primary tumor. In cancer cells, the periodic variation of nuclear stiffness during the cell cycle provides a functional link between efficient translocation and proliferation. However, the mechanical framework completing this picture remains unexplored. Here, the Fucci2 reporter was expressed in various human epithelial cancer cells to resolve their cell cycle phase transition. The corresponding tractions were captured by a recently developed reference-free confocal traction-force microscopy platform. The combined approach was conducive to the analysis of phase-dependent force variation at the level of individual integrin contacts. Detected forces were invariably higher in the G1 and early S phases than in the ensuing late S/G2, and locally colocalized with high levels of paxillin phosphorylation. Perturbation of paxillin phosphorylation at focal adhesions, obtained through the biochemical inhibition of focal adhesion kinase (FAK) or the transfection of nonphosphorylatable or phosphomimetic paxillin mutants, significantly diminished the force transmitted to the substrate. These data demonstrate a reproducible modulation of force transmission during the cell cycle progression of cancer cells, instrumental to their invasion of dense environments. In addition, they delineate a model in which paxillin phosphorylation supports the mechanical maturation of adhesions relaying forces to the substrate. |
format | Online Article Text |
id | pubmed-6254576 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-62545762019-02-04 Cell cycle–dependent force transmission in cancer cells Panagiotakopoulou, Magdalini Lendenmann, Tobias Pramotton, Francesca Michela Giampietro, Costanza Stefopoulos, Georgios Poulikakos, Dimos Ferrari, Aldo Mol Biol Cell Articles The generation of traction forces and their transmission to the extracellular environment supports the disseminative migration of cells from a primary tumor. In cancer cells, the periodic variation of nuclear stiffness during the cell cycle provides a functional link between efficient translocation and proliferation. However, the mechanical framework completing this picture remains unexplored. Here, the Fucci2 reporter was expressed in various human epithelial cancer cells to resolve their cell cycle phase transition. The corresponding tractions were captured by a recently developed reference-free confocal traction-force microscopy platform. The combined approach was conducive to the analysis of phase-dependent force variation at the level of individual integrin contacts. Detected forces were invariably higher in the G1 and early S phases than in the ensuing late S/G2, and locally colocalized with high levels of paxillin phosphorylation. Perturbation of paxillin phosphorylation at focal adhesions, obtained through the biochemical inhibition of focal adhesion kinase (FAK) or the transfection of nonphosphorylatable or phosphomimetic paxillin mutants, significantly diminished the force transmitted to the substrate. These data demonstrate a reproducible modulation of force transmission during the cell cycle progression of cancer cells, instrumental to their invasion of dense environments. In addition, they delineate a model in which paxillin phosphorylation supports the mechanical maturation of adhesions relaying forces to the substrate. The American Society for Cell Biology 2018-10-15 /pmc/articles/PMC6254576/ /pubmed/30113874 http://dx.doi.org/10.1091/mbc.E17-12-0726 Text en © 2018 Panagiotakopoulou et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 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. |
spellingShingle | Articles Panagiotakopoulou, Magdalini Lendenmann, Tobias Pramotton, Francesca Michela Giampietro, Costanza Stefopoulos, Georgios Poulikakos, Dimos Ferrari, Aldo Cell cycle–dependent force transmission in cancer cells |
title | Cell cycle–dependent force transmission in cancer cells |
title_full | Cell cycle–dependent force transmission in cancer cells |
title_fullStr | Cell cycle–dependent force transmission in cancer cells |
title_full_unstemmed | Cell cycle–dependent force transmission in cancer cells |
title_short | Cell cycle–dependent force transmission in cancer cells |
title_sort | cell cycle–dependent force transmission in cancer cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254576/ https://www.ncbi.nlm.nih.gov/pubmed/30113874 http://dx.doi.org/10.1091/mbc.E17-12-0726 |
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