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 epithelial differentiation. Data from model systems suggest that E-cadherin is a potent invasion/tumor suppressor of breast cancer. Consistent with this role in breast cancer progression, partial or complete loss of E-cadherin expression has been found to correlate with poor prognosis in breast cancer patients. The E-cadherin gene (CDH1) is located on human chromosome 16q22.1, a region frequently affected with loss of heterozygosity in sporadic breast cancer. Invasive lobular breast carcinomas, which are typically completely E-cadherin-negative, often show inactivating mutations in combination with loss of heterozygosity of the wild-type CDH1 allele. Mutations were found 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 heterogeneous loss of E-cadherin expression, associated with epigenetic transcriptional 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.
Berx
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Molecular Cell Biology Unit, Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology (VIB) - Ghent University, Ghent, Belgium.
Van Roy
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F
D015703:Antigens, CD; D001943:Breast Neoplasms / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D005260:Female; D005656:Fungal Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D005656:Fungal Proteins