Assessing a Drosophila Metastasis Model in Mouse and Human Breast Cancer
Annual rept. 23 Apr 2008-22 Apr 2009
WASHINGTON UNIV ST LOUIS MO SCHOOL OF MEDICINE
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In this Synergy award, we proposed to bring compounds identified with a novel screening method to standard mouse breast cancer assays. We developed CskSrc Drosophila models to explore specific aspects of overgrowth and metastasis. Both Src and the Csk paralog Chk have been implicated in breast cancer metastasis. We propose to test the hypothesis that drugs identified in our novel Drosophila wing model of tumor invasive proliferation and metastasis- targeting the effects of activated Src- will show efficacy in a mouse model of breast cancer and metastasis. The overall goal of this proposal is to validate the findings from a Drosophila metastasis model in murine and human breast cancers. Specifically, we will examine the interactions of epithelial tumor cells with bordering non-malignant epithelial cells, and whether these interactions alter the metastatic potential of cells at the tumor boundary. Several critical signaling pathways specific to this interaction have been identified in a Drosophila whole animal genetic screen. We propose to validate these pathways in mouse and human breast cancers, and to extend the Drosophila search for new factors. The long term goals of this proposal will be to identify critical targets involved in tumor progression and breast cancer metastasis using the power of forward genetics in Drosophila, and to develop novel murine breast cancer models of metastasis that can be used to screen new genes and therapeutics targeted to breast cancer metastasis Figure 1.
- Medicine and Medical Research