Integrin-dependent actomyosin contraction regulates epithelial cell scattering
Integrin-dependent actomyosin contraction regulates epithelial cell scattering
复制标题
DOI：
10.1083/jcb.200506152
复制
发表时间：
2005-10-10
影响因子：
7.8
通讯作者：
Waterman-Storer, CM
中科院分区：
文献类型：
--
作者：
de Rooij, J;Kerstens, A;Waterman-Storer, CM
Madin-Darby犬肾细胞在体外的分散模拟了发育、癌细胞侵袭和转移过程中上皮-间质转化的关键方面。散射是由肝细胞生长因子（HGF）诱导的，被认为涉及钙粘蛋白依赖性细胞-细胞连接的破坏。与层粘连蛋白1相比，胶原蛋白和纤维连接蛋白的散射增强，表明整合素和细胞-细胞连接之间可能存在串扰。我们发现HGF不会引起e -钙粘蛋白功能的任何可检测的下降，但会增加整合素介导的粘附。延时成像T提示细胞-细胞连接处的张力可能会破坏细胞-细胞粘附。改变细胞外基质蛋白的密度和类型表明，散射与更强的整合素粘附和肌球蛋白调节轻链磷酸化增加有关。为了直接测试整合素依赖性牵引力的作用，衬底柔顺性发生了变化。与更柔顺的基材相比，产生高牵引力的刚性基材促进了散射。我们得出结论，在上皮细胞散射过程中，整合素依赖的肌动球蛋白牵引力介导了细胞-细胞粘附的破坏。
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 T 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.