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The YAP1-NPM1 nuclear complex regulates MYC and reveals a targetable oncogenic node

Abdulrahman M Dwead1,2, Marwah M Al-Mathkour1,3, Maxim Khanov4

  • 1Department of Biological Sciences and Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA 30314, USA.

Iscience
|May 11, 2026
PubMed

Insights

Yes-associated protein 1 (YAP1) and nucleophosmin 1 (NPM1) form a complex in prostate cancer. Inhibiting NPM1 disrupts this axis, suppressing cancer growth and offering new therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Yes-associated protein 1 (YAP1) and nucleophosmin 1 (NPM1) are proteins with known cellular functions.
  • Their combined roles in cancer development are not well understood.

Purpose of the Study:

  • To investigate the interaction between YAP1 and NPM1 in prostate cancer.
  • To determine the functional consequences of this interaction and its potential as a therapeutic target.

Main Methods:

  • Proteomics, co-immunoprecipitation, proximity ligation, and GST-pulldown assays were used to detect the YAP1-NPM1 complex.
  • Androgen signaling modulation was studied in androgen receptor-positive cells.
  • Genetic and pharmacologic inhibition of NPM1 was performed.
  • Prostate tumor samples were analyzed using immunological and computational methods.

Main Results:

  • YAP1 and NPM1 form a direct nuclear protein complex in prostate cancer cells and tissues.
  • Androgen signaling influences the YAP1-NPM1 interaction.
  • NPM1 inhibition disrupts the complex, reduces YAP1 and MYC expression, and inhibits cell proliferation and motility.
  • Elevated YAP1 and NPM1 expression and interaction correlate with prostate cancer progression.

Conclusions:

  • The YAP1-NPM1 axis is a critical regulator in prostate cancer, integrating oncogenic pathways.
  • This axis represents a potential therapeutic vulnerability.
  • Targeting the YAP1-NPM1 axis may improve androgen receptor-directed therapies for advanced prostate cancer.
Keywords:
biochemistrybiological sciencescancercell biology

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