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PCTAIRE1 phosphorylates p27 and regulates mitosis in cancer cells

Teruki Yanagi1, Maryla Krajewska1, Shu-ichi Matsuzawa2

  • 1Sanford-Burnham Medical Research Institute, La Jolla, California.

Cancer Research
|September 11, 2014
PubMed

Insights

PCTAIRE1, a cyclin-dependent kinase relative, drives cancer cell growth by affecting p27 stability and mitosis. Silencing PCTAIRE1 inhibits tumor growth, suggesting it as a potential cancer therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • PCTAIRE1, a distant relative of cyclin-dependent kinases, is linked to spermatogenesis and neuronal development but unstudied in cancer.
  • Its role in cancer progression and potential as a therapeutic target remain unexplored.

Purpose of the Study:

  • To investigate the role of PCTAIRE1 in cancer.
  • To identify PCTAIRE1's interacting partners and elucidate its mechanism of action in cancer cells.
  • To evaluate PCTAIRE1 as a potential therapeutic target for cancer treatment.

Main Methods:

  • RNA interference (RNAi)-mediated silencing of PCTAIRE1 in various cancer cell lines (prostate, breast, cervical).
  • Yeast two-hybrid screening to identify PCTAIRE1 interacting proteins.
  • In vitro kinase assays to determine PCTAIRE1's phosphorylation activity on p27.
  • Cell cycle analysis and centrosome dynamics assessment.
  • Mouse xenograft models for in vivo tumor growth assessment.
  • Analysis of PCTAIRE1 expression in clinical tumor samples.

Main Results:

  • PCTAIRE1 is expressed in prostate, breast, and cervical cancer cells, and its silencing inhibits cancer cell growth.
  • PCTAIRE1 silencing leads to aberrant mitosis due to centrosome defects, specifically in cancer cells.
  • PCTAIRE1 interacts with and phosphorylates tumor suppressor p27 at Ser10, modulating its stability and accumulation.
  • Silencing PCTAIRE1 suppresses tumor growth in a prostate cancer xenograft model.
  • PCTAIRE1 is highly expressed in primary breast and prostate tumors compared to normal tissues.

Conclusions:

  • PCTAIRE1 plays a crucial role in regulating p27 stability, mitosis, and tumor growth in various cancers.
  • PCTAIRE1's specific involvement in cancer cell proliferation and its high expression in tumors highlight its potential as a therapeutic target.

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