Expression of Inappropriate Cadherins in Human Breast Carcinomas

摘要

E-cadherin is a transmembrane protein that mediates calcium-dependent cell-cell adhesion and plays a role in maintaining the normal phenotype of epithelial cells. Decreased expression of E-cadherin is correlated with increased invasiveness of breast cancer. Inappropriate expression of a non- epithelial cadherin, such as N-cadherin, by an epithelial cell has been shown to down-regulate E-cadherin expression and contribute to cell motility. In this study we explored the possibility that expression of non-epithelial cadherins may be correlated with increased cellular motility and invasion in breast cancer cells. We showed that (1) N-cadherin promotes motility and invasion in breast cancer cells; (2) decreased expression of E-cadherin does not correlate with invasion in breast cancer cells; (3) N-cadherin expression correlates with invasion and motility in breast cancer cells and plays a direct role in promoting motility; (4) forced expression of E-cadherin in invasive, N-cadherin positive cells does not reduce their invasive capacity; (5) forced expression of N-cadherin in non-invasive, E-cadherin-positive cells produces an invasive cell even though these cells continue to express E-cadherin; (6) N-cadherin-dependent motility may be mediated by fibroblast growth factor receptor signaling; and (7) the domain on N-cadherin that is responsible for increased invasion resides in the 4th extracellular repeat domain.