Mechanism of Cadherin Switching in Breast Carcinoma
Abstract
During the progression of cancer, cells often undergo an epithelial-mesenchymal transition (EMT). This is associated with trading intercellular adhesion for a motile phenotype, as cells lose E-cadherin and gain the pro- migratory N-cadherin. While this process of cadherin switching has been described previously, the underlying molecular mechanism has yet to be elucidated. Here, we examine the role of p12O catenin (pl2Octn) and the Kaiso transcription factor as mediators of cadherin switching in breast cancer. It is proposed that EMT-induced loss of E-cadherin results in the interaction of pl2Octn with kaiso transcription factor to induce expression of N- Cadherin. This is supported by the presence of putative Kaiso binding sites in the N-cadherin promoter. Moreover, pl2Octn co-localizes with kaiso in cells that have lost E-cadherin but not in those that maintain its expression. To confirm this role for pl2Octn, co-immunoprecipitation of this protein with Kaiso will be utilized in an EMT model of breast cancer. Further, siRNA will be employed to demonstrate the necessity of these two proteins in EMT-induced cadherin switching. These experiments will describe a reasonable and novel mechanism for cadherin in breast cancer, while lending itself directly to the design of new therapies targeted at inhibiting breast cancer metastasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA435244
Entities
People
- David I. Bellovin
Organizations
- Beth Israel Deaconess Medical Center