Acute and Chronic Cadmium Exposure Promotes E-Cadherin Degradation in MCF7 Breast Cancer Cells

作者：Ponce Esmeralda; Louie Maggie C^*; Sevigny Mary B

来源：Molecular Carcinogenesis, 2015, 54(10): 1014-1025.

DOI：10.1002/mc.22170

• cadmium
• breast cancer
• E-cadherin
• beta-catenin

Cadmium is an environmental carcinogen that usually enters the body at minute concentrations through diet or cigarette smoke and bioaccumulates in soft tissues. In past studies, cadmium has been shown to contribute to the development of more aggressive cancer phenotypes including increased cell migration and invasion. This study aims to determine if cadmium exposure-both acute and chronic-contributes to breast cancer progression by interfering with the normal functional relationship between E-cadherin and beta-catenin. An MCF7 breast cancer cell line (MCF7-Cd) chronically exposed to 10(-7) M CdCl2 was previously developed and used as a model system to study chronic exposures, whereas parental MCF7 cells exposed to 10(-6) M CdCl2 for short periods of time were used to study acute exposures. Cadmium exposure of MCF7 cells led to the degradation of the E-cadherin protein via the ubiquitination pathway. This resulted in fewer E-cadherin/beta-catenin complexes and the relocation of active beta-catenin to the nucleus, where it interacted with transcription factor TCF-4 to modulate gene expression. Interestingly, only cells chronically exposed to cadmium showed a significant decrease in the localization of beta-catenin to the plasma membrane and an increased distance between cells. Our data suggest that cadmium exposure promotes breast cancer progression by (1) down-regulating E-cadherin, thus decreasing the number of Ecadherin/beta-catenin adhesion complexes, and (2) enhancing the nuclear translocation of beta-catenin to increase expression of cancer-promoting proteins (i. e., c-Jun and cyclin D1).

• 出版日期2015-10