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Tick-Tock: Cancer Cell Division Cycle Clocks Strike Midnight.

Scott C Schuyler1,2, Hsin-Yu Chen1, Tran Thi Bao Nguyen1

  • 1Department of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 333, Taiwan.

International Journal of Molecular Sciences
|July 12, 2025
PubMed
Summary
This summary is machine-generated.

Aneuploid cancer cells may be more vulnerable to forced overgrowth than healthy cells. This study proposes targeting the anaphase-promoting complex/cyclosome (APC/C) to induce overgrowth and test this hypothesis in cancer therapy.

Keywords:
anaphase-promoting complex/cyclosome (APC/C)cancercell division cycleheat-shock protein 90 (HSP90)proteotoxic stress

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Area of Science:

  • Cell Biology
  • Cancer Biology
  • Molecular Biology

Background:

  • Eukaryotic cells maintain uniform size through coordinated mass doubling and division.
  • Cancer cells, often aneuploid, experience proteotoxic stress and altered unfolded-protein response.
  • Heat-shock proteins (HSPs) are crucial for managing protein folding under stress.

Purpose of the Study:

  • To hypothesize that aneuploid cancer cells are more sensitive to forced overgrowth than diploid cells.
  • To explore targeting the anaphase-promoting complex/cyclosome (APC/C) to induce forced overgrowth in cancer cells.
  • To propose novel combination therapies for cancer treatment.

Main Methods:

  • Hypothesizing differential sensitivity to forced overgrowth based on ploidy.
  • Suggesting modulation of the anaphase-promoting complex/cyclosome (APC/C) activity.
  • Proposing experimental combinations of APC/C inhibitors with HSP90 inhibitors.

Main Results:

  • Forced overgrowth increases protein production and the window for protein misfolding/aggregation.
  • Cancer cells' proteotoxic stress may exacerbate negative effects of forced overgrowth.
  • APC/C inhibition is proposed as a strategy to induce forced overgrowth.

Conclusions:

  • Aneuploid cancer cells might be uniquely susceptible to forced overgrowth.
  • Targeting APC/C activity offers a potential therapeutic strategy.
  • Investigating combinations of APC/C and HSP90 inhibitors may yield new cancer treatments.