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Integrin-dependent actomyosin contraction regulates epithelial cell scattering.

de Rooij J, Kerstens A, Danuser G, Schwartz MA, Waterman-Storer CM - J. Cell Biol. (2005)

Bottom Line: Scattering is enhanced on collagen and fibronectin, as compared with laminin1, suggesting possible cross talk between integrins and cell-cell junctions.Rigid substrates that produce high traction forces promoted scattering, in comparison to more compliant substrates.We conclude that integrin-dependent actomyosin traction force mediates the disruption of cell-cell adhesion during epithelial cell scattering.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

ABSTRACT
The scattering of Madin-Darby canine kidney cells in vitro mimics key aspects of epithelial-mesenchymal transitions during development, carcinoma cell invasion, and metastasis. Scattering is induced by hepatocyte growth factor (HGF) and is thought to involve disruption of cadherin-dependent cell-cell junctions. Scattering is enhanced on collagen and fibronectin, as compared with laminin1, suggesting possible cross talk between integrins and cell-cell junctions. We show that HGF does not trigger any detectable decrease in E-cadherin function, but increases integrin-mediated adhesion. Time-lapse imaging suggests that tension on cell-cell junctions may disrupt cell-cell adhesion. Varying the density and type of extracellular matrix proteins shows that scattering correlates with stronger integrin adhesion and increased phosphorylation of the myosin regulatory light chain. To directly test the role of integrin-dependent traction forces, substrate compliance was varied. Rigid substrates that produce high traction forces promoted scattering, in comparison to more compliant substrates. We conclude that integrin-dependent actomyosin traction force mediates the disruption of cell-cell adhesion during epithelial cell scattering.

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Focal adhesions and F-actin on different types of ECM. Paxillin and F-actin localization in cells grown on 3 μg/ml Cn, 10 μg/ml Fn, or 10 μg/ml Ln1. In cells on Fn and Cn, larger peripheral focal adhesions are associated with dense actin bundles. On Ln1, peripheral focal adhesions and actin bundles are nearly absent, although elongated central adhesions are associated with actin bundles.
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fig5: Focal adhesions and F-actin on different types of ECM. Paxillin and F-actin localization in cells grown on 3 μg/ml Cn, 10 μg/ml Fn, or 10 μg/ml Ln1. In cells on Fn and Cn, larger peripheral focal adhesions are associated with dense actin bundles. On Ln1, peripheral focal adhesions and actin bundles are nearly absent, although elongated central adhesions are associated with actin bundles.

Mentions: To directly investigate cytoskeletal organization under different ECM conditions, cells were fixed and stained for F-actin and the focal adhesion protein paxillin. On Fn or Cn, which promote efficient adhesion and rapid scattering, large, intensely stained focal adhesions extended to within a few micrometers of the cell edge (Fig. 5). In contrast, on Ln1, where adhesion was less efficient and scattering was slower, the cell periphery had only weak paxillin staining of small, thin, elongated adhesions, whereas more intensely stained, elongated structures were concentrated in the central region of the cells. Accordingly, in cells on Fn or Cn, F-actin bundles connecting to focal adhesions were thick and straight, whereas F-actin bundles in the periphery of cells on Ln1 were very thin, and F-actin structures connecting to the focal adhesions were often not discernible. Focal adhesion size is proportional to tension in the connecting actin bundles, whereas reduced cytoskeletal tension results in small focal adhesions (Schoenwaelder and Burridge, 1999; Ballestrem et al., 2001). Thus, these results indicate that efficient scattering correlates with a distinct cytoskeletal phenotype that suggests high transmission of tension to the cell periphery.


Integrin-dependent actomyosin contraction regulates epithelial cell scattering.

de Rooij J, Kerstens A, Danuser G, Schwartz MA, Waterman-Storer CM - J. Cell Biol. (2005)

Focal adhesions and F-actin on different types of ECM. Paxillin and F-actin localization in cells grown on 3 μg/ml Cn, 10 μg/ml Fn, or 10 μg/ml Ln1. In cells on Fn and Cn, larger peripheral focal adhesions are associated with dense actin bundles. On Ln1, peripheral focal adhesions and actin bundles are nearly absent, although elongated central adhesions are associated with actin bundles.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171213&req=5

fig5: Focal adhesions and F-actin on different types of ECM. Paxillin and F-actin localization in cells grown on 3 μg/ml Cn, 10 μg/ml Fn, or 10 μg/ml Ln1. In cells on Fn and Cn, larger peripheral focal adhesions are associated with dense actin bundles. On Ln1, peripheral focal adhesions and actin bundles are nearly absent, although elongated central adhesions are associated with actin bundles.
Mentions: To directly investigate cytoskeletal organization under different ECM conditions, cells were fixed and stained for F-actin and the focal adhesion protein paxillin. On Fn or Cn, which promote efficient adhesion and rapid scattering, large, intensely stained focal adhesions extended to within a few micrometers of the cell edge (Fig. 5). In contrast, on Ln1, where adhesion was less efficient and scattering was slower, the cell periphery had only weak paxillin staining of small, thin, elongated adhesions, whereas more intensely stained, elongated structures were concentrated in the central region of the cells. Accordingly, in cells on Fn or Cn, F-actin bundles connecting to focal adhesions were thick and straight, whereas F-actin bundles in the periphery of cells on Ln1 were very thin, and F-actin structures connecting to the focal adhesions were often not discernible. Focal adhesion size is proportional to tension in the connecting actin bundles, whereas reduced cytoskeletal tension results in small focal adhesions (Schoenwaelder and Burridge, 1999; Ballestrem et al., 2001). Thus, these results indicate that efficient scattering correlates with a distinct cytoskeletal phenotype that suggests high transmission of tension to the cell periphery.

Bottom Line: Scattering is enhanced on collagen and fibronectin, as compared with laminin1, suggesting possible cross talk between integrins and cell-cell junctions.Rigid substrates that produce high traction forces promoted scattering, in comparison to more compliant substrates.We conclude that integrin-dependent actomyosin traction force mediates the disruption of cell-cell adhesion during epithelial cell scattering.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

ABSTRACT
The scattering of Madin-Darby canine kidney cells in vitro mimics key aspects of epithelial-mesenchymal transitions during development, carcinoma cell invasion, and metastasis. Scattering is induced by hepatocyte growth factor (HGF) and is thought to involve disruption of cadherin-dependent cell-cell junctions. Scattering is enhanced on collagen and fibronectin, as compared with laminin1, suggesting possible cross talk between integrins and cell-cell junctions. We show that HGF does not trigger any detectable decrease in E-cadherin function, but increases integrin-mediated adhesion. Time-lapse imaging suggests that tension on cell-cell junctions may disrupt cell-cell adhesion. Varying the density and type of extracellular matrix proteins shows that scattering correlates with stronger integrin adhesion and increased phosphorylation of the myosin regulatory light chain. To directly test the role of integrin-dependent traction forces, substrate compliance was varied. Rigid substrates that produce high traction forces promoted scattering, in comparison to more compliant substrates. We conclude that integrin-dependent actomyosin traction force mediates the disruption of cell-cell adhesion during epithelial cell scattering.

Show MeSH
Related in: MedlinePlus