Quinocarmycin analog DX-52-1 inhibits cell migration and targets radixin, disrupting interactions of radixin with actin and CD44.
Journal Article (Journal Article)
In the course of screening for new small-molecule modulators of cell motility, we discovered that quinocarmycin (also known as quinocarcin) 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 antimigratory activity. Small interfering RNA-mediated silencing of radixin expression reduces the rate of cell migration. Finally, we found that DX-52-1 disrupts radixin's ability to interact with both actin and the cell adhesion molecule CD44.
- Kahsai, AW; Zhu, S; Wardrop, DJ; Lane, WS; Fenteany, G
- September 2006
Volume / Issue
- 13 / 9
Start / End Page
- 973 - 983
International Standard Serial Number (ISSN)
Digital Object Identifier (DOI)
- United States