DRF as a Cholesterol Dependent Regulator of Src in Prostate Cancer
Final rept. 15 Dec 2005-14 Sep 2009
CHILDREN'S HOSPITAL MEDICAL CENTER BOSTON MA
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This project focuses on the novel finding from our group that the diaphanous-related formin protein DRF3 is a signaling molecule positioned downstream from the EGF receptor that intersects with the sine kinase Src in prostate cancer cells. Formins are effectors of small Rho-family GTPases like and provide a direct link between activated membrane receptors and the actin cytoskeleton. They also regulated by a large number of other activators including Src homology 3 SH3-containing adaptor proteins and Src family kinases, and can therefore serve as signal integrating platforms inside cell. Evidence was presented in the original proposal that the EGFRDrf3 Src signaling circuit appears to traverse cholesterol-rich lipid raft membranes in prostate cancer cells. Lipid rafts are choleterol- and sphingolipid-enriched membrane microdomains that serve as signal transduction platforms sequestering and excluding signaling proteins and by harboring pre-formed multiprotein complexes. 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 of--signals that flow through lipid raft microdomains. Several new lines of evidence consistent this hypothesis have been produced in year 2 and are described and summarized in this report.
- Medicine and Medical Research