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Programmed cell death protein 4 down-regulates Y-box binding protein-1 expression via a direct interaction with

Masaki Shiota1, Hiroto Izumi, Akihide Tanimoto

  • 1Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan.

Cancer Research
|March 26, 2009
PubMed

Insights

Programmed cell death protein 4 (PDCD4) inhibits cancer cell growth by down-regulating Y-box binding protein-1 (YB-1) through interaction with the transcription factor Twist1. PDCD4 influences chemoresistance, impacting cancer treatment strategies.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Programmed cell death protein 4 (PDCD4) is implicated in cell growth regulation, but its precise mechanisms remain unclear.
  • Understanding PDCD4's role in transcription and translation is crucial for cancer therapy development.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which PDCD4 regulates cell growth.
  • To investigate the interaction between PDCD4, Twist1, and its target gene YB-1.
  • To assess the impact of PDCD4 on cancer cell chemoresistance.

Main Methods:

  • Investigated the direct interaction between PDCD4 and the transcription factor Twist1.
  • Analyzed the effect of PDCD4 on Twist1 DNA binding and YB-1 expression.
  • Conducted immunohistochemical analysis on clinical prostate cancer specimens.
  • Evaluated the sensitivity of PDCD4-overexpressing cells to various chemotherapeutic agents.

Main Results:

  • PDCD4 directly binds to the DNA binding domain of Twist1, inhibiting its activity and down-regulating YB-1 expression.
  • An inverse correlation between nuclear PDCD4 and YB-1 levels was observed in prostate cancer tissues.
  • PDCD4-mediated growth suppression was reversed by increased Twist1 or YB-1 expression.
  • PDCD4 overexpression enhanced sensitivity to cisplatin and paclitaxel, but not etoposide or 5-fluorouracil.

Conclusions:

  • PDCD4 negatively regulates YB-1 expression through interaction with Twist1, impacting cancer cell proliferation.
  • PDCD4 plays a significant role in modulating cancer cell chemoresistance.
  • These findings offer potential therapeutic targets for cancer treatment by modulating PDCD4-Twist1-YB-1 signaling.

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