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Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells
15:53

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells

Published on: August 21, 2013

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Simultaneous reduction of MAD2 and BUBR1 expression induces mitotic spindle alterations associated with p53 dependent

Laura Lentini1, Desirèe Piscitello, Lorena Veneziano

  • 1Department of Biological Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo Viale delle Scienze, Palermo, 90128, Italy.

Cell Biology International
|April 2, 2014
PubMed

Insights

Tumor aneuploidy, often caused by chromosomal instability (CIN), is linked to weakened mitotic checkpoints. Depleting SAC proteins MAD2 and BUBR1 in tumor cells induced cell death, highlighting p53

Area of Science:

  • Cell Biology
  • Cancer Research
  • Genetics

Background:

  • Aneuploidy is a hallmark of human tumors, often stemming from chromosomal instability (CIN).
  • The Spindle Assembly Checkpoint (SAC) is crucial for preventing aneuploidy during mitosis.
  • Mechanisms underlying aneuploidy and its tolerance in cancer remain incompletely understood.

Purpose of the Study:

  • To investigate cellular responses to aneuploidy induced by simultaneous depletion of SAC proteins.
  • To elucidate the role of p53 in response to severe mitotic checkpoint perturbation.

Main Methods:

  • Near-diploid tumor cells were used to study aneuploidy.
  • RNA interference was employed to deplete SAC proteins MAD2 and BUBR1.
  • Cell cycle progression, cell death, and ploidy were analyzed.

Main Results:

  • Individual depletion of MAD2 or BUBR1 led to defective mitosis and aneuploidy.
  • Co-depletion of MAD2 and BUBR1 induced cell cycle arrest, cell death, and aneuploidy.
  • Simultaneous depletion resulted in hyperdiploid cells and p53 stabilization, suggesting p53 activation.

Conclusions:

  • Strong perturbation of the mitotic checkpoint by MAD2 and BUBR1 co-depletion triggers cell cycle arrest and death.
  • The p53 pathway is essential for mediating cell cycle arrest and death in response to severe mitotic errors.
  • p53 activation prevents the propagation of aneuploid cells, acting as a safeguard against CIN-driven tumorigenesis.
Keywords:
cell cyclecell deathchromosomes

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