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 beta-catenin and E-cadherin are mislocalized, forming novel structures perpendicular to cell-cell junctions. c-Src is associated with beta-catenin/E-cadherin complexes and beta-catenin tyrosine phosphorylation is enhanced. Blocking c-Src tyrosine kinase activity decreased beta-catenin tyrosine phosphorylation and restored localization of beta-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.