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Nucleophosmin interacts with FOXM1 and modulates the level and localization of FOXM1 in human cancer cells

Uppoor G Bhat1, Ramasamy Jagadeeswaran1, Marianna Halasi2

  • 1Department of Medicine, University of Illinois, Chicago, Illinois 60612.

The Journal of Biological Chemistry
|October 8, 2011
PubMed

Insights

The oncogenic transcription factor FOXM1 interacts with protein NPM in cancer cells. Targeting this interaction may offer a new cancer therapy strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The transcription factor FOXM1 is overexpressed in many human cancers.
  • The multifunctional protein NPM is also overexpressed in various human tumors.
  • The interaction between FOXM1 and NPM in cancer is not well understood.

Purpose of the Study:

  • To investigate the interaction between FOXM1 and NPM in cancer cells.
  • To determine the functional consequences of this interaction.
  • To explore the potential of targeting this interaction for cancer therapy.

Main Methods:

  • Mass spectrometric analysis
  • Coimmunoprecipitation and glutathione S-transferase pull-down assays
  • Immunofluorescence microscopy
  • Gene knockdown experiments
  • Cell culture and in vivo tumor growth assays

Main Results:

  • NPM forms a complex with FOXM1, with specific interaction regions identified.
  • NPM knockdown leads to decreased FOXM1 levels and altered intracellular localization.
  • Knockdown of either FOXM1 or NPM inhibits cancer cell growth and tumor growth in vivo.
  • Overexpression of FOXM1 can rescue the effects of NPM knockdown.

Conclusions:

  • NPM interacts with FOXM1 in cancer cells, maintaining its level and localization.
  • The NPM-FOXM1 interaction is crucial for cancer cell proliferation and tumor growth.
  • Targeting the NPM-FOXM1 interaction presents a potential novel therapeutic strategy for cancer treatment.

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