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.
Zhao
Yan
Y
Department of Pharmacology, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Planas-Silva
Maricarmen D
MD
D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D000081247:CSK Tyrosine-Protein Kinase; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004965:Estrogen Antagonists / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D006801:Humans; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism; D051176:beta Catenin / Q000737:chemistry / Q000378:metabolism; D019061:src-Family Kinases
D015820:Cadherins; D004965:Estrogen Antagonists; D020847:Estrogen Receptor Modulators; D051176:beta Catenin; D013629:Tamoxifen; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human