Cell migration inhibitors identified by quantitative phase-contrast microscopy screening

Cell migration inhibitors identified by quantitative phase-contrast microscopy screening

By use of hepatocyte growth factor induced scattering of MDCK cells as a model system, a commercially available chemical library of small-molecule inhibitors was screened for the capacity to affect cell-cell dissociation and cell migration, both important components of cellular invasion. Among the 29 identified inhibitors of scattering, eight specifically affected cell migration while nine inhibited cell-cell dissociation. In addition to previously known pathways, including c-src and PI3-kinase, also less established targets, such as cdk1 and S6 kinase were identified and then verified by RNAi. In addition, indirubin compounds inhibited cell migration while nonsteriodal anti-inflammatory drugs inhibited cell-cell disassociation. This is an example of how a quantitative microscopy based approach can contribute to the identification of novel pathways potentially important for cell invasion. This is also an example of how this approach can be used to discover novel inhibitors with a potential effect on invasion related diseases, such as cancer and inflammation.

PubMed

Seventh Framework Programme

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