E-Cadherin, beta -Catenin and cadmium carcinogenesis

Cadmium (Cd(2+)) is an important industrial and environmental pollutant that has been classified as a human carcinogen. Studies reported in the literature indicate that cadmium may play a role in both the initiation of cancer, by activating oncogenes, and in the progression of cancer, by increasing the metastatic potential of existing cancer cells. However, the mechanisms underlying these effects have yet to be elucidated. Recent studies from our laboratory have shown that cadmium can disrupt the tight junctions between many types of epithelial cells by interfering with the normal function of E-cadherin, a Ca(2+)-dependent cell adhesion molecule that plays a key role in epithelial cell-cell adhesion. This finding may be especially significant because a large volume of evidence indicates that the disruption of E-cadherin-mediated cell adhesion can trigger the beta-catenin-mediated activation of oncogenes in epithelial cells and increase the invasive potential of existing epithelial-derived cancers. The hypothesis that we are proposing is that the cadmium-induced disruption of E-cadherin dependent cell-cell junctions may represent a pivotal step in both the initiation of cancer by cadmium and in the tumor promoting actions of cadmium.