To verify this assumption, we knocked down CLDN6 in SB431542-treated MCF-7 and SKBR-3 cells and found knocking down CLDN6 abrogated the inhibitory effects of SB431542 on EMT, migration and invasion of breast cancer cells, indicating CLDN6 is the key regulator downstream of the SMAD2/DNMT1/CLDN6 pathway. Here, SMAD2 is linked to breast carcinoma.