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Kahsai, A.W. et al.

Quinocarmycin Analog DX-52-1 Inhibits Cell Migration and Targets Radixin, Disrupting Interactions of Radixin with Actin and CD44.

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.[1]

References

Quinocarmycin Analog DX-52-1 Inhibits Cell Migration and Targets Radixin, Disrupting Interactions of Radixin with Actin and CD44. Kahsai, A.W., Zhu, S., Wardrop, D.J., Lane, W.S., Fenteany, G. Chem. Biol. (2006) [Pubmed]

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