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Cell–cell junctions are pulled apart by cytoskeletal traction forces during epithelial cell scattering. The results from De Rooij et al. (page 153) suggest that down-regulation of the cell–cell glue, E-cadherin, is not required in this process.$ E+ U2 m- i2 y2 O" x) T
$ I/ f! n+ ?4 [# UDuring cell scattering induced by hepatocyte growth factor (HGF), cell contacts must necessarily be disrupted. The down–regulation of E-cadherin expression or function by HGF has thus been the focus of attention for researchers interested in how epithelial cells acquire migratory abilities. Now, the new findings indicate that cadherins remain functional but are forcibly ripped apart.9 Z! s; z% b7 J+ l, d
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HGF-treated cells that did not migrate away from their neighbors maintained functional E-cadherin adhesions. New adhesions were also built as scattering cells made new encounters. Though working properly, E-cadherin adhesions were rapidly lost just as cells started migrating.According to the authors, the cell–cell junctions are pulled apart by forces stemming from cell–matrix adhesions. Thick actin bundles were seen between matrix-attached focal adhesions in distant parts of the cell and those adjacent to cadherin-based junctions. Active myosin, which contracts actin fibers, localized along these bundles upon HGF treatment.
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Strong integrin-based adhesions to collagen and fibronectin supported fast, efficient scattering. The weaker bonds of laminin were less efficient in inducing scattering, even though laminin supported the fastest migration velocity.5 A1 ~; M4 R9 D: t X0 U) F! \' }; h
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Some tension is required to maintain cell–cell adhesions, but clearly too much can be their downfall. The authors are thus curious to know how adhesions measure tension levels and how E-cadherin junctions are pulled apart. Only thin actin filaments were seen linking the cytoskeleton to a cell–cell junction under tension. As thin filaments are probably not strong enough to break cadherin bonds, perhaps a stiff membrane helps out.. D. g# ~/ l4 K! Z9 h7 P+ j% y
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As scattering is a model for metastasis, the results are supported by recent findings from others that increased stiffness promotes malignant behavior (Paszek et al. 2005. Cancer Cell. 8:241–254). De Rooij believes that contraction forces are also likely to control the transient lapses in endothelial cell–cell adhesions that allow immune cells to leave the vasculature.(Myosin (red) contraction of actin (green) |
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发表于 2009-3-6 08:44
发表于 2026-4-8 12:56
