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-β, 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.

• Authors: Zhongguo Shan, Zhengxi Wei, Zahir A Shaikh
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 356 Pg. 36-43 (10 01 2018) ISSN: 1096-0333 [Electronic] United States
• PMID: 30030096 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Antigens, CD
• CDH1 protein, human
• CDH2 protein, human
• Cadherins
• Cation Transport Proteins
• RNA, Small Interfering
• Transforming Growth Factor beta
• metal transporting protein 1
• Cadmium
• Iron

Topics

• Antigens, CD (biosynthesis)
• Cadherins (biosynthesis)
• Cadmium (toxicity)
• Cation Transport Proteins (antagonists & inhibitors, biosynthesis)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Epithelial-Mesenchymal Transition (drug effects)
• Female
• Gene Expression Regulation, Neoplastic
• Homeostasis (drug effects)
• Humans
• Iron (metabolism)
• RNA, Small Interfering (pharmacology)
• Transforming Growth Factor beta (antagonists & inhibitors)
• Triple Negative Breast Neoplasms (pathology)