Suppression of ferroportin expression by cadmium stimulates proliferation, EMT, and migration in triple-negative breast cancer cells.

ABSTRACT

Cadmium (Cd) has been linked to a variety of cancers, including breast cancer; however, the molecular mechanism of its carcinogenic activity is not fully understood. To this end, the present study investigated the roles of ferroportin (FPN), a prognostic marker of breast cancer, in Cd-induced stimulation of cell proliferation and cell migration. Triple-negative MDA-MB-231 cells were treated with 1-3 µM Cd. The cells exhibited significant reduction in FPN expression and concomitant increase in iron concentration. Cells treated with Cd for 8 weeks displayed elevated proliferative and migratory activities which were inversely related with FPN expression. Reduced FPN expression also resulted in EMT as indicated by an increase in the expression of E-cadherin, and a decrease in the expression of N-cadherin, Twist and Slug. Further investigation revealed that Cd suppressed FPN expression at least partially by activating TGF-ß, a known regulator of FPN expression. Taken together, these results indicate that Cd-induced stimulation of MDA-MB-231 cell proliferation, EMT, and migration is brought about by suppression of FPN expression and associated disruption of iron homeostasis.