Mislocalization of cell–cell adhesion complexes in tamoxifen-resistant breast cancer cells with elevated c-Src tyrosine kinase activity

c-Src activation has been implicated in metastasis of tamoxifen-resistant breast cancer. Here we investigated how c-Src activity affects cell adhesion using a tamoxifen-resistant variant of MCF-7 cells (MTR-3) containing elevated c-Src activity. In MTR-3 cells, adhesion proteins β-catenin and E-cadherin are mislocalized, forming novel structures perpendicular to cell–cell junctions. c-Src is associated with β-catenin/E-cadherin complexes and β-catenin tyrosine phosphorylation is enhanced. Blocking c-Src tyrosine kinase activity decreased β-catenin tyrosine phosphorylation and restored localization of β-catenin and E-cadherin at cell–cell junctions. These findings suggest that inhibition of c-Src signaling may prevent metastasis of tamoxifen-resistant breast cancer.