Endosulfan triggers epithelial-mesenchymal transition via PTP4A3-mediated TGF-β signaling pathway in prostate cancer cells.

Endosulfan is a persistent organochlorine pesticide that bioaccumulates in human body through the food chain and thus represents a potential risk to public health. Despite epidemiological studies, the molecular mechanisms underlying the carcinogenic effects of endosulfan in the prostate remain poorly understood. In this study, we investigated the effect of endosulfan on epithelial-mesenchymal transition (EMT) in human prostate cancer PC3 and DU145 cells. Endosulfan induced alterations of EMT biomarkers, reflecting repression of E-cadherin expression and induction of fibronectin, snail2, ZEB2, Twist1 and Vimentin. The expression of Protein-tyrosine Phosphatase 4A3 (PTP4A3) at mRNA and protein levels was upregulated by endosulfan. PTP4A3 inhibitor reversed the changes of EMT biomarkers, PTP4A3 and p-Smad2/Smad2, but did not affect the upregulation of Cleaved-Notch1 and Jagged1 in endosulfan-exposed cells. Endosulfan promoted cell migration and invasion, which were rescued by specific inhibitors for PTP4A3, TGF-β signaling and Notch signaling, respectively. These findings suggest that endosulfan promoted cell migration and invasion with the induction of EMT through PTP4A3-mediated TGF-β signaling pathway in prostate cancer cells.