RRC ID 55992
著者 Panagiotakopoulou M, Lendenmann T, Pramotton FM, Giampietro C, Stefopoulos G, Poulikakos D, Ferrari A.
タイトル Cell cycle-dependent force transmission in cancer cells.
ジャーナル Mol Biol Cell
Abstract 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.
巻・号 29(21)
ページ 2528-2539
公開日 2018-10-15
DOI 10.1091/mbc.E17-12-0726
PMID 30113874
PMC PMC6254576
MeSH Biomechanical Phenomena / drug effects Cell Cycle* / drug effects Cell Movement / drug effects Cell Proliferation / drug effects Drug Resistance, Neoplasm / drug effects Focal Adhesion Protein-Tyrosine Kinases / metabolism HEK293 Cells HeLa Cells Humans MCF-7 Cells Neoplasm Invasiveness Neoplasms / pathology* Paxillin / metabolism Phenotype Phosphorylation / drug effects Tamoxifen / pharmacology
IF 3.905
引用数 8
リソース情報
ヒト・動物細胞 HeLa/Fucci2(RCB2867)