DRF3 as a Cholesterol-Dependent Regulator of Src in Prostate Cancer
Annual rept. 15 Dec 2005-14 Dec 2006
CHILDREN'S HOSPITAL MEDICAL CENTER BOSTON MA
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This project focuses on the novel finding from our group that the formin protein, Drf3, is a signaling molecule positioned downstream from the EGF receptor that intersects with the tyrosine kinase Src in prostate cancer cells. Formins bind small GTPases and have been implicated in actin cytoskeletal remodeling. Evidence was presented in the original proposal that the EGFR Drf3 Src signaling circuit appears to traverse cholesterol-rich lipid raft membranes in prostate cancer cells. Lipid rafts are cholesterol-and sphingolipid-enriched membrane microdomains that serve as signal transduction platforms by sequestering and excluding signaling proteins and by harboring pre-formed multi-protein complexes. We have hypothesized in this project, and in our published work in this area, that cholesterol accumulation in prostate cancer cells may promote oncogenesis by altering the nature of andor the types of signals that flow through lipid raft microdomains. Several new lines of evidence consistent with our hypothesis have been produced in year 1 of the project and are described and summarized in this progress report.
- Medicine and Medical Research