Centrosome amplification can initiate tumorigenesis in flies.
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.
Basto
Renata
R
The Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK. renata.basto@curie.fr
Brunk
Kathrin
K
Vinadogrova
Tatiana
T
Peel
Nina
N
Franz
Anna
A
Khodjakov
Alexey
A
Raff
Jordan W
JW
D000818:Animals; D030801:Animals, Genetically Modified; D018385:Centrosome / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism; D007814:Larva / Q000166:cytology / Q000235:genetics; D008938:Mitosis; D017346:Protein Serine-Threonine Kinases; D008941:Spindle Apparatus
D029721:Drosophila Proteins; C066696:ncd protein, Drosophila; D049452:Green Fluorescent Proteins; D017346:Protein Serine-Threonine Kinases; C522064:Sak protein, Drosophila; D016547:Kinesins