The role of cadherin-mediated adhesion in breast cancer.

Abstract

The cell adhesion molecule E-cadherin is expressed on the basolateral surfaces of normal mammary epithelial cells and is lost in a subset of breast cancers. Loss of E-cadherin expression has been postulated to facilitate tumor cell detachment from a primary tumor ultimately leading to metastasis. In this paper, I review the published in vitro data that initially supported this "invasion suppressor" role for E-cadherin as well as more recent in vitro and in vivo data showing that E-cadherin-positive tumor cells can metastasize. I examine other molecules required for E-cadherin function and discuss how defects in the expression or function of these molecules might alter E-cadherin function in E-cadherin-positive tumor cells. For example, loss of expression or function of catenins, intracellular molecules that interact with E-cadherin, can result in the loss of E-cadherin-mediated adhesion and a more invasive phenotype. Altered phosphorylation of E-cadherin or catenins can also influence E-cadherin function. Finally, expression of other cell surface molecules such as mucins may interfere with E-cadherin function. The collective effect of these molecules on the adhesive phenotype of breast cancer cells may be one determinant of metastatic potential.