Co-operative effect of c-Src and ezrin in deregulation of cell-cell contacts and scattering of mammary carcinoma cells |
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Authors: | Elliott Bruce E Qiao Hui Louvard Daniel Arpin Monique |
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Institution: | Queen's University Cancer Research Institute, Division of Cancer Biology and Genetics, Queen's University, Kingston, ON, Canada K7L 3N6. elliottb@post.queensu.ca |
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Abstract: | 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. |
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Keywords: | ezrin c‐Src cadherins cell–cell contacts cell scattering carcinomas |
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