Snail induces dormancy in disseminated luminal type A breast cancer through Src inhibition.

Breast cancer includes biologically distinct subtypes, and the time between rise in distant metastases and overall survival for the subtypes are different. The mechanisms involved in these differences in tumor metastasis remain to be elucidated. Here, we demonstrated that, luminal type A breast cancer cells, such as MCF7 and T47D, when overexpressed with active mutant form of Snail (6SA-Snail) increased in the expression of EMT markers such as Vimentin, N-cadherin and Fibronectin but decreased in the expression of E-cadherin, compared to control vectors or wild type Snail. Moreover, this mutant increased in migration and invasion ability, while decreased in the capacity to survive and form spheres in tumor spheroid medium. Luciferase reporter assay and chromatin immunoprecipitation followed by quantitative PCR (ChIP-qPCR) analysis revealed that Snail downregulated Src by binding to the E-box of Src promoter. Human luminal type A breast cancer specimens showed an inverse correlation between Vimentin and Src expression. Most importantly, downregulation of Src by Snail was not found in breast cancer cell types other than luminal type A. Therefore, elucidation of the differences in signaling pathways involved in controlling migration, invasion and colonization may have a therapeutically beneficial effect on breast cancer treatment. AJCR