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The transcription factor FOXM1 is a cellular target of the natural product thiostrepton

Nagaratna S Hegde1, Deborah A Sanders, Raphaël Rodriguez

  • 1Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.

Nature Chemistry
|August 24, 2011
PubMed

Insights

The natural product thiostrepton directly interacts with the FOXM1 transcription factor, inhibiting its binding to DNA. This research highlights the potential for targeting transcription factors like FOXM1 with small molecules for cancer therapy.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Drug Discovery

Background:

  • Transcription factors regulate gene expression but are challenging drug targets.
  • FOXM1 (Forkhead box M1) is a transcription factor implicated in cancer progression.
  • The natural product thiostrepton is known to inhibit FOXM1 activity.

Purpose of the Study:

  • To investigate the direct interaction between thiostrepton and FOXM1.
  • To elucidate the molecular mechanism by which thiostrepton affects FOXM1 function.
  • To assess the potential of targeting FOXM1 with small molecules.

Main Methods:

  • Biophysical analyses to study protein-ligand interactions.
  • Cellular experiments in MCF-7 human breast cancer cells.
  • Assessment of FOXM1 binding to genomic DNA targets.

Main Results:

  • Thiostrepton directly binds to the FOXM1 protein.
  • Biophysical data provide insights into the mode of action.
  • Thiostrepton inhibits FOXM1's ability to bind its target DNA sequences.

Conclusions:

  • Transcription factors, including FOXM1, are druggable targets.
  • Thiostrepton's interaction with FOXM1 provides a molecular basis for its anti-cancer effects.
  • This study supports the development of small molecules targeting the FOXM1 family for cancer treatment.

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