Co-operative effect of c-Src and ezrin in deregulation of cell-cell contacts and scattering of mammary carcinoma cells
Co-operative effect of c-Src and ezrin in deregulation of cell-cell contacts and scattering of mammary carcinoma cells
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DOI：
10.1002/jcb.20033
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发表时间：
2004-05-01
影响因子：
4
通讯作者：
Arpin, M
中科院分区：
文献类型：
--
作者：
Elliott, BE;Qiao, H;Arpin, M
非受体酪氨酸激酶c-Src在许多人类癌症类型中被激活，并诱导基于钙粘蛋白的细胞-细胞接触和肌动蛋白细胞骨架的失调。由于ezrin，一种蛋白质，交联的质膜与肌动蛋白细胞骨架，往往在人类癌症中过度表达，并参与细胞粘附，运动性，和细胞散射，因此，我们研究是否c-Src合作与ezrin在调节细胞-细胞接触在小鼠乳腺癌细胞系，SP1。SP1细胞过度表达野生型埃兹蛋白，或激活的c-Src突变体，形成松散的聚集体，分散自发时，在塑料板上。当野生型埃兹蛋白和活化的c-Src共表达时，散射增加，细胞-细胞接触被破坏，并且细胞聚集被阻止。用c-Src家族激酶抑制剂PP 2预处理部分恢复了表达活化的c-Src和野生型埃兹蛋白的细胞的聚集，表明c-Src家族激酶与埃兹蛋白在调节细胞-细胞接触中协同作用。此外，具有显性负功能的ezrin的截短的NH 2-末端结构域的表达阻断了活化的c-Src的细胞散射效应，并促进了粘性细胞-细胞接触的形成。总之，这些结果表明c-Src和ezrin之间的协同作用，在失调的细胞-细胞接触和增强乳腺癌细胞的散射。(C)2004 Wiley-Liss，Inc.
The non-receptor tyrosine kinase c-Src is activated in many human cancer types, and induces deregulation of cadherin-based cell-cell contacts and actin cytoskeleton. Because ezrin, a protein which cross-links the plasma membrane with the actin cytoskeleton, is often over-expressed in human cancers, and participates in cell adhesion, motility, and cell scattering, we therefore investigated whether c-Src co-operates with ezrin in regulating cell-cell contacts in a murine mammary carcinoma cell line, SP1. SP1 cells over-expressing wild type ezrin, or an activated c-Src mutant, formed loose aggregates which scattered spontaneously when plated on plastic. When wild type ezrin and activated c-Src were co-expressed, scattering was increased, cell-cell contacts disrupted, and cell aggregation prevented. Pre-treatment with the c-Src family kinase inhibitor PP2 partially restored aggregation of cells expressing activated c-Src and wild type ezrin, indicating that c-Src family kinases act co-operatively with ezrin in regulating cell-cell contacts. Furthermore, expression of a truncated NH2-terminal domain of ezrin, which has dominant negative function, blocked the cell scattering effect of activated c-Src and promoted formation of cohesive cell-cell contacts. Together, these results suggest co-operativity between c-Src and ezrin in deregulation of cell-cell contacts and enhancing scattering of mammary carcinoma cells. (C) 2004 Wiley-Liss, Inc.