AEI 19 |
| Cell migration is a central feature of many processes, including embryonic development, tissue repair, immune function, and angiogenesis. Furthermore, aberrant cell migration contributes to pathologies such as cancer cell invasion and metastasis, making the control of cell migration a potential point of therapeutic intervention in cancer treatment. In the course of screening for new small-molecule modulators of cell motility, we discovered that quinocarmycin analog DX-52-1 is an inhibitor of epithelial cell migration. While it has been assumed that the main target of DX-52-1 is DNA, we identified and confirmed radixin as the relevant molecular target of DX-52-1 in the cell. Radixin is a member of the ezrin/radixin/moesin family of membrane-actin cytoskeleton linker proteins that also participate in signal transduction pathways. DX-52-1 binds specifically and covalently to the C-terminal region of radixin, which contains the domain that interacts with actin filaments. Overexpression of radixin in cells abrogates their sensitivity to DX-52-1's anti-migratory activity. Small interfering RNA-mediated silencing of radixin expression reduces the rate of cell migration. DX-52-1 disrupts radixin's ability to interact with both actin and the cell adhesion protein CD44, thus defining a novel mode of action for a small-molecule inhibitor of cell migration. * Correspondence : gabriel.fenteany@uconn.edu |
|
Academic Employment Initiative
8:00 PM-10:00 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Sci-Mix
Academic Employment Initiative |