Six1-Eya-Dach Network in Breast Cancer
Abstract
The Six1 homeodomain-containing transcription factor stimulates the proliferation and survival of progenitor cells and plays a role in the epithelial to mesenchymal transition (EMT) during development. Using cell culture and mouse models, we have previously shown that Six1 not only promotes proliferation and survival, contributing to tumorigenesis, but also upregulates the TGF pathway, brings about an EMT-like transformation, and promotes metastasis. There are no known intrinsic activation or repression domains in Six1. The Eya family (Eya1-4), coactivators of Six1, play important roles in Six1-mediated transcriptional activation in development. Here, we preliminarily show that Eya2 is required for Six1-induced upregulation of the TGF? pathway as well as for most Six1-induced epithelial to mesenchymal transition (EMT) phenotypes. These results suggest that Eya2 is a critical coactivator that is necessary for Six1-induced tumorigenic properties. Thus, as Six1 and Eya are not normally expressed in most adult tissues, the Six1-Eya interaction may be a valuable future therapeutic target for the 50% of primary breast tumors and 90% of metastatic lesions that overexpress Six1.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2009
- Accession Number
- ADA505204
Entities
People
- Susan Farabaugh
Organizations
- University of Colorado Health