Computer Aided Identification of Small Molecules Disrupting uPAR/α5β1- Integrin Interaction: A New Paradigm for Metastasis Prevention
2009

Disrupting uPAR/Integrin Interaction to Prevent Cancer Metastasis

Sample size: 13 publication 10 minutes Evidence: high

Author Information

Author(s): Chaurasia Pratima, Mezei Mihaly, Zhou Ming-Ming, Ossowski Liliana

Primary Institution: Mount Sinai School of Medicine

Hypothesis

Can small molecules disrupt the interaction between uPAR and α5β1-integrin to prevent cancer metastasis?

Conclusion

The study found that two small molecules can disrupt the uPAR/integrin interaction, leading to reduced ERK activation and inhibited tumor growth and metastasis.

Supporting Evidence

  • 68 compounds were identified that could potentially disrupt the uPAR/integrin interaction.
  • Two lead compounds significantly inhibited ERK activation and tumor growth in vivo.
  • Disruption of the uPAR/integrin interaction led to a state of dormancy in cancer cells.

Takeaway

Researchers found two tiny molecules that can stop cancer cells from growing by blocking a specific interaction between two proteins, which helps keep the cancer cells sleepy instead of making them grow.

Methodology

The study used computational docking to screen a library of 13,000 small molecules, identifying 68 candidates that could disrupt the uPAR/integrin interaction, followed by in vitro and in vivo assays to test their efficacy.

Potential Biases

Potential bias in the selection of compounds and the specific cancer model used.

Limitations

The study primarily focused on a specific cancer model and may not be generalizable to all cancer types.

Statistical Information

P-Value

p<0.0001

Statistical Significance

p<0.0001

Digital Object Identifier (DOI)

10.1371/journal.pone.0004617

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication