In this breast cancer progression system, increased activity of the TGF-beta-Smad2 signaling pathway is associated with the DNA methylation-mediated silencing of a gene subset including CDH1. Along with the mesenchymal cancer cell phenotype, inhibition of TGF-beta signaling is able to revert the methylation status and expression of select genes by inhibiting the DNMT1 and DNMT3B binding to the CDH1 and other promoter regions [85]. This evidence concerns the gene CDH1 and breast cancer.