Zhao Yan, Planas-Silva Maricarmen D
Department of Pharmacology, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Cancer Lett. 2009 Mar 18;275(2):204-12. doi: 10.1016/j.canlet.2008.10.022. Epub 2008 Nov 20.
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.
c-Src激活与他莫昔芬耐药乳腺癌的转移有关。在此，我们使用c-Src活性升高的MCF-7细胞他莫昔芬耐药变体（MTR-3），研究了c-Src活性如何影响细胞黏附。在MTR-3细胞中，黏附蛋白β-连环蛋白和E-钙黏蛋白定位错误，形成垂直于细胞-细胞连接的新结构。c-Src与β-连环蛋白/E-钙黏蛋白复合物相关，且β-连环蛋白酪氨酸磷酸化增强。阻断c-Src酪氨酸激酶活性可降低β-连环蛋白酪氨酸磷酸化，并恢复β-连环蛋白和E-钙黏蛋白在细胞-细胞连接处的定位。这些发现表明，抑制c-Src信号传导可能预防他莫昔芬耐药乳腺癌的转移。
