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Co‐operative effect of c‐Src and ezrin in deregulation of cell–cell contacts and scattering of mammary carcinoma cells
Author(s) -
Elliott Bruce E.,
Qiao Hui,
Louvard Daniel,
Arpin Monique
Publication year - 2004
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20033
Subject(s) - ezrin , proto oncogene tyrosine protein kinase src , microbiology and biotechnology , cell , tyrosine protein kinase csk , cell migration , cell adhesion , cancer cell , chemistry , src family kinase , cytoskeleton , kinase , biology , sh3 domain , cancer , biochemistry , genetics
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 NH 2 ‐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. © 2004 Wiley‐Liss, Inc.