Co-operative effect of c-Src and ezrin in deregulation of cell-cell contacts and scattering of mammary carcinoma cells

J Cell Biochem. 2004 May 1;92(1):16-28. doi: 10.1002/jcb.20033.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CSK Tyrosine-Protein Kinase
  • Cadherins / metabolism
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Carcinoma / physiopathology
  • Cell Adhesion
  • Cell Aggregation
  • Cell Communication
  • Cell Line, Tumor
  • Cell Movement*
  • Cytoskeletal Proteins
  • Female
  • Fibronectins / chemistry
  • Immunoprecipitation
  • Mammary Neoplasms, Experimental / metabolism*
  • Mammary Neoplasms, Experimental / pathology
  • Mammary Neoplasms, Experimental / physiopathology
  • Mice
  • Mutation / genetics
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Plastics / chemistry
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Transfection
  • Tyrosine / metabolism
  • src-Family Kinases

Substances

  • Cadherins
  • Cytoskeletal Proteins
  • Fibronectins
  • Phosphoproteins
  • Plastics
  • ezrin
  • Tyrosine
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human