The Src-induced mesenchymal state in late-stage colon cancer cells
The Src-induced mesenchymal state in late-stage colon cancer cells
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DOI：
10.1159/000084511
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发表时间：
2005-01-01
影响因子：
2.7
通讯作者：
Frame, MC
中科院分区：
文献类型：
--
作者：
Avizienyte, E;Brunton, VG;Frame, MC
上皮癌细胞中升高的Src激酶的一个主要功能是驱动与间充质转化和转移相关的粘附变化[Jones et al.，Br J Cancer 2002;87：1128-1135]。在这里，我们回顾了最近的工作，描述Src诱导的形状变化，以及所涉及的机制，在来自结肠癌转移模型的细胞。这些细胞中的Src活性与整合素粘附的形成和动态调节以及E-钙粘蛋白依赖性细胞-细胞接触的解体相关。此外，Src诱导的E-钙粘蛋白失调需要整联蛋白信号传导[Avizienyte et al.，Nat Cell Biol 2002;4：632-638]，证明了Src诱导的整合素和钙粘蛋白相关粘附变化之间的复杂相互依赖性。整合素诱导的信号与Src合作，导致钙粘蛋白依赖性细胞-细胞接触的失调，包括MEK/ERK和MLCK/肌球蛋白活性的激活。该途径的抑制抑制了纤连蛋白上形成的整联蛋白复合物，同时促进E-钙粘蛋白重新分布到细胞-细胞接触位点[ Avizienyte et al.，Mol Biol Cell 2004; 15：2794-2803]。此外，在表达N-钙粘蛋白的胚胎成纤维细胞中（由于这些细胞保持成纤维细胞形态，其通常是弥漫性细胞质），抑制整合素信号传导和抑制MEK/ERK/MLCK/肌球蛋白途径使N-钙粘蛋白重新定位于细胞-细胞接触。因此，我们最近的数据意味着一个重要的，也许是一般的，空间控制的收缩性抑制正常的钙粘蛋白定位和诱导间充质样表型的作用。版权所有（C）2005 S. Karger AG，巴塞尔。
One major function of elevated Src kinase in epithelial cancer cells is to drive adhesion changes that are associated with the mesenchymal transition and metastasis [Jones et al., Br J Cancer 2002;87:1128-1135]. Here we review recent work that describes Src-induced shape changes, and the mechanisms involved, in cells derived from a model of colon cancer metastasis. Src activity in these cells is associated with formation and dynamic regulation of integrin adhesions and disorganization of E-cadherin-dependent cell-cell contacts. Furthermore, Src-induced deregulation of E-cadherin requires integrin signalling [Avizienyte et al., Nat Cell Biol 2002;4:632-638], demonstrating a complex interdependence between integrin- and cadherin-associated adhesion changes induced by Src. The integrin- induced signals that co-operate with Src to cause deregulation of cadherin-dependent cell-cell contacts include activation of the MEK/ERK and MLCK/myosin activities. Inhibition of this pathway suppresses integrin complexes formed on fibronectin, while promoting E-cadherin redistribution to sites of cell-cell contacts [ Avizienyte et al., Mol Biol Cell 2004; 15: 2794-2803]. Also, in embryonic fibroblasts that express N-cadherin (which is normally diffusely cytoplasmic as these cells maintain a fibroblastic morphology) suppressing integrin signalling and inhibiting the MEK/ERK/MLCK/myosin pathway relocalizes N-cadherin to cell-cell contacts. Our recent data therefore imply an important, and perhaps general, role for spatially controlled contractility in suppressing normal cadherin localization and inducing a mesenchymal-like phenotype. Copyright (C) 2005 S. Karger AG, Basel.