Computer aided identification of small molecules disrupting uPAR/alpha5beta1--integrin interaction: a new paradigm for metastasis prevention.

ABSTRACT:

Background

Disseminated dormant cancer cells can resume growth and eventually form overt metastases, but the underlying molecular mechanism responsible for this change remains obscure. We previously established that cell surface interaction between urokinase receptor (uPAR) and alpha5beta1-integrin initiates a sequel of events, involving MAPK-ERK activation that culminates in progressive cancer growth. We also identified the site on uPAR that binds alpha5beta1-integrin. Disruption of uPAR/integrin interaction blocks ERK activation and forces cancer cells into dormancy.

Methods and principle findings

Using a target structure guided computation docking we identified 68 compounds from a diversity library of 13,000 small molecules that were predicted to interact with a previousl

SUBMITTER: Chaurasia P 

PROVIDER: S-EPMC2643475 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature