Background Claudin-6 is a protein component of tight junctions and its expression could downregulate the malignant phenotype of breast carcinoma.Here we investigated the mechanisms of claudin-6 induced human MCF-7 breast cancer cells apoptosis,invasion,and migration.Methods Terminal deoxyribonucleotide transferase-mediated nick-end labeling assay and Annexin-V/PI double stain assay were carried out to evaluate apoptosis.Inhibitors of each pathway were used to inactivate the signaling pathways.The expression of claudin-6 and phosphate p38,Erk 1/2 and Akt protein levels was confirmed by West blotting analysis.Invasive and migratory traits of claudin-6 expressing cells were determined by Boyden chamber invasion assay and monolayer wound-healing assay.Results Cells with high-level expression of claudin-6 had a higher rate of apoptosis than control cells.West blotting assay showed that by contrast to control groups,p38 pathways were more activated in claudin-6 expressing cells.However,after inhibitor SB203580 treatment,the activation status could be significantly counteracted.Furthermore,by applying inhibitors to the apoptotic rate,invasive and migratory traits were also recovered in cells with claudin-6 expression.Conclusion Claudin-6 may function through p38 mitogen-activated protein kinase pathway,of which inhibition may reverse claudin-6-induced cell apoptosis,invasion,and migration.