Predicting Sensitivity of Breast Tumors to Src-Targeted Therapies through Assessment of Cas/Src/BCAR3 Activity
Abstract
Purpose: The purpose of this research is to assess the role of a signaling pathway comprised of the protein tyrosine kinase c-Src (Src) and two adaptor molecules, Cas and BCAR3, in promoting breast tumor growth, metastasis and therapeutic resistance toward Src-targeted small molecule inhibitors. Scope: The proposed research employs 2- and 3-dimensional tissue culture models, transplantable mouse models of breast cancer, and analysis of human breast tumor samples. Major Findings: Key results from the first year of support include (1) BCAR3 and Cas are coexpressed in multiple subtypes of breast cancer but not in normal mammary epithelial cells;(2) the Cas/Src/BCAR3 signaling complex regulates breast tumor cell adhesion dynamics and invasion; (3) BCAR3 is an essential regulator of tumor initiation in a transplantable murine model of breast cancer; and (4) BCAR3 is essential for the ability of mammary epithelial cells to develop ex vivo into budding breast organoids. These data provide evidence for the crucial activity of the Cas/Src/BCAR3 signaling node in breast cancer progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2016
- Accession Number
- AD1025935
Entities
People
- Amy H. Bouton
Organizations
- University of Virginia