Journal article
Cell cycle–dependent force transmission in cancer cells
- Panagiotakopoulou, Magdalini Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zurich, CH-8092 Zürich, Switzerland
- Lendenmann, Tobias Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zurich, CH-8092 Zürich, Switzerland
- Pramotton, Francesca Michela Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zurich, CH-8092 Zürich, Switzerland
- Giampietro, Costanza Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zurich, CH-8092 Zürich, Switzerland
- Stefopoulos, Georgios Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zurich, CH-8092 Zürich, Switzerland
- Poulikakos, Dimos Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zurich, CH-8092 Zürich, Switzerland
- Ferrari, Aldo EMPA, Swiss Federal Laboratories for Materials Science and Technology, 8600 Dübendorf, Switzerland
Published in:
- Molecular Biology of the Cell. - American Society for Cell Biology (ASCB). - 2018, vol. 29, no. 21, p. 2528-2539
English
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.
- Language
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- English
- Open access status
- hybrid
- Identifiers
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- DOI 10.1091/mbc.e17-12-0726
- ISSN 1059-1524
- Persistent URL
- https://folia.unifr.ch/global/documents/283940
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