Centrosome Amplification Can Initiate Tumorigenesis in Flies

Cell. 2008 Jun 13;133(6):1032-42. doi: 10.1016/j.cell.2008.05.039.

Abstract

Centrosome amplification is a common feature of many cancer cells, and it has been previously proposed that centrosome amplification can drive genetic instability and so tumorigenesis. To test this hypothesis, we generated Drosophila lines that have extra centrosomes in approximately 60% of their somatic cells. Many cells with extra centrosomes initially form multipolar spindles, but these spindles ultimately become bipolar. This requires a delay in mitosis that is mediated by the spindle assembly checkpoint (SAC). As a result of this delay, there is no dramatic increase in genetic instability in flies with extra centrosomes, and these flies maintain a stable diploid genome over many generations. The asymmetric division of the larval neural stem cells, however, is compromised in the presence of extra centrosomes, and larval brain cells with extra centrosomes can generate metastatic tumors when transplanted into the abdomens of wild-type hosts. Thus, centrosome amplification can initiate tumorigenesis in flies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Centrosome / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / genetics*
  • Green Fluorescent Proteins / metabolism
  • Kinesin / metabolism
  • Larva / cytology
  • Larva / genetics
  • Mitosis
  • Protein-Serine-Threonine Kinases
  • Spindle Apparatus

Substances

  • Drosophila Proteins
  • ncd protein, Drosophila
  • Green Fluorescent Proteins
  • Protein-Serine-Threonine Kinases
  • Sak protein, Drosophila
  • Kinesin