The E-cadherin/catenin complex: an important gatekeeper in breast cancer tumorigenesis and malignant progression

E-cadherin is a cell-cell adhesion protein fulfilling a prominent role in e pithelial differentiation. Data from model systems suggest that E-cadherin is a potent invasion/tumor suppressor of breast cancer. Consistent with thi s role in breast cancer progression, partial or complete loss of E-cadherin expression has been found to correlate with poor prognosis in breast cance r patients. The E-cadherin gene (CDH1) is located on human chromosome 16q22 .1, a region frequently affected with loss of heterozygosity in sporadic br east cancer. Invasive lobular breast carcinomas, which are typically comple tely E-cadherin-negative, often show inactivating mutations in combination with loss of heterozygosity of the wild-type CDH1 allele. Mutations were fo und at early noninvasive stages, thus associating E-cadherin mutations with loss of cell growth control and defining CDH1 as the tumor suppressor for the lobular breast cancer subtype. Ductal breast cancers in general show he terogeneous loss of E-cadherin expression, associated with epigenetic trans criptional downregulation. It is proposed that the microenvironment at the invasive front is transiently downregulating E-cadherin transcription. This can be associated with induction of nonepithelial cadherins.