Assessing a Drosophila Metastasis Model in Mouse and Human Breast Cancer
Abstract
We propose to combine our expertise to target a process that is critical to breast cancer metastasis that is likely conserved in flies, mice and humans. The advantages of addressing the question of metastasis through the combined expertise of the Cagan and Weilbaecher labs is that we will use the powerful genetic tools provided by Drosophila that will identify key genetic pathways critical to tumor cell migration and metastasis that can be rapidly and rigorously tested. This a real time, in vivo dynamic screen that occurs in a whole organism. Tumors develop in the epithelial layer of the wing and the genetics of tumor cell invasion and migration throughout the organism can be modeled in real time, and genetically manipulated in large scale genetic screens. Dr. Weilbaecher's laboratory will take advantage of the genetic knowledge gained from the Drosophila metastasis models in the development of an improved breast cancer metastasis mouse model. Dr. Cagan's laboratory will be provided with mammalian human and murine breast cancers to validate their genetic and pharmacologic anti-metastasis strategies. Jointly, Drs. Cagan and Weilbaecher propose to develop novel therapeutics targeted to the metastatic process. In year one, we have identified 6 compounds that decrease metastasis in Drosophila metastasis model and decrease viability of mammalian breast cancer cells in vitro. We have validated the compound Cyclopamine, a hedgehog inhibitor, to block lung metastases in murine breast cancer xenograft and will use this as a template for testing other candidate therapeutic compounds from fly to mouse. Finally, we have uncovered a previously unknown and important connection between Src and Hedgehog signaling in mediating metastasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2008
- Accession Number
- ADA490655
Entities
People
- Katherine N. Weilbaecher
- Ross Cagan
Organizations
- University of Washington