E-cadherin, beta-catenin and cadmium carcinogenesis

Cadmium (Cd2+) is an important industrial and environmental pollutant that has been classified as a human carcinogen. Studies reported in the literatu re indicate that cadmium may play a role in both the initiation of cancer, by activating oncogenes, and in the progression of cancer, by increasing th e metastatic potential of existing cancer cells. However, the mechanisms un derlying these effects have yet to be elucidated. Recent studies from our l aboratory have shown that cadmium can disrupt the tight junctions between m any types of epithelial cells by interfering with the normal function of E- cadherin, a Ca2+-dependent cell adhesion molecule that plays a key role in epithelial cell-cell adhesion. This finding may be especially significant b ecause a large volume of evidence indicates that the disruption of E-cadher in-mediated cell adhesion can trigger the beta -catenin-mediated activation of oncogenes in epithelial cells and increase the invasive potential of ex isting epithelial-derived cancers. The hypothesis that we are proposing is that the cadmium-induced disruption of E-cadherin dependent cell-cell junct ions may represent a pivotal step in both the initiation of cancer by cadmi um and in the tumor promoting actions of cadmium. (C) 2001 Harcourt Publish ers Ltd.