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A tumor suppressor role of the Bub3 spindle checkpoint protein after apoptosis inhibition

Sara Morais da Silva1, Tatiana Moutinho-Santos, Claudio E Sunkel

  • 1Instituto de Biologia Molecular e Celular, Universidade do Porto, 4099 Porto, Portugal. sara.silva@ibmc.up.pt

The Journal of Cell Biology
|April 24, 2013
PubMed

Insights

A Drosophila model reveals that Bub3, a spindle assembly checkpoint (SAC) gene, functions as a tumor suppressor. Its non-kinetochore role is crucial for preventing neoplastic growth and aneuploidy in solid tumors.

Area of Science:

  • Cell Biology
  • Genetics
  • Cancer Research

Background:

  • Aneuploidy, or abnormal chromosome numbers, is common in solid tumors, yet mutations in mitotic checkpoint genes are rare in human cancers.
  • The spindle assembly checkpoint (SAC) ensures accurate chromosome segregation during cell division.

Purpose of the Study:

  • To investigate the role of SAC genes, specifically Bub3, in tumorigenesis using a Drosophila model.
  • To determine if aneuploidy alone is sufficient to drive tumor formation.

Main Methods:

  • Knockdown of SAC genes and inhibition of apoptosis in Drosophila wing imaginal discs.
  • Tumorigenesis assays involving transplantation of Bub3-deficient cells.
  • Investigating the role of Bub3's kinetochore binding in proliferation.

Main Results:

  • Bub3-deficient tumors lacking apoptosis exhibited neoplastic growth, aneuploidy, and high proliferative potential.
  • Aneuploidy induced by CENP-E knockdown without apoptosis inhibition did not cause hyperplasia.
  • Disrupting Bub3's kinetochore binding did not induce hyperproliferation, suggesting a non-kinetochore function.

Conclusions:

  • Aneuploidy is not sufficient to cause hyperplasia; SAC deficiency plays a critical role in tumorigenesis.
  • Bub3 possesses a non-kinetochore-dependent tumor suppressor function, independent of its role in the SAC.

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