Quinocarmycin analog DX-52-1 inhibits cell migration and targets radixin, disrupting interactions of radixin with actin and CD44.

Published

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.

Full Text

Duke Authors

Cited Authors

  • Kahsai, AW; Zhu, S; Wardrop, DJ; Lane, WS; Fenteany, G

Published Date

  • September 2006

Published In

Volume / Issue

  • 13 / 9

Start / End Page

  • 973 - 983

PubMed ID

  • 16984887

Pubmed Central ID

  • 16984887

International Standard Serial Number (ISSN)

  • 1074-5521

Digital Object Identifier (DOI)

  • 10.1016/j.chembiol.2006.07.011

Language

  • eng

Conference Location

  • United States