Predicting Sensitivity of Breast Tumors to Src-Targeted Therapies through Assessment of Cas/Src/BCAR3 Activity
Technical Report,15 Sep 2015,14 Sep 2016
VIRGINIA UNIV CHARLOTTESVILLE CHARLOTTESVILLE United States
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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 cells2 the CasSrcBCAR3 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 CasSrcBCAR3 signaling node in breast cancer progression.
- Medicine and Medical Research