The Cadherin Interaction as a Rate Limiting Step in Breast Cancer Metastasis to the Liver
Abstract
Epithelial-cadherin's (E-cadherin) transcriptional silencing in most advanced tumors, due to promoter methylation, enables tumor cells to disseminate from the primary mass. However, E-cadherin-positive metastatic carcinoma foci do originate from mainly E-cadherin-negative primaries. We demonstrate that co-culture of hepatocytes with invasive breast cancer cells lacking E-cadherin triggers an epigenetic reversion in the breast cancer cells resulting in demethylation of the E-cadherin promoter and subsequent expression on the protein level. Further, we show that the E-cadherin ligation between breast cancer cells and hepatocytes is functional and activates the canonical MAPK pathway and Akt pathway in these cancer cells. Our epigenetic-reversion hypothesis for E-cadherin represents not only a paradigm shift in the current thinking that absence of E-cadherin is a fundamental issue, but would also reveal new strategies to combat the initial stages of metastatic disease in breast cancer patients.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2007
- Accession Number
- ADA469554
Entities
People
- Christopher R. Shepard
Organizations
- University of Pittsburgh