Centrosome amplification can initiate tumorigenesis in flies
Centrosome amplification can initiate tumorigenesis in flies
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DOI：
10.1016/j.cell.2008.05.039
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发表时间：
2008-06-13
期刊：
影响因子：
64.5
通讯作者：
Raff, Jordan W.
中科院分区：
文献类型：
--
作者：
Basto, Renata;Brunk, Kathrin;Raff, Jordan W.
中心体扩增是许多癌细胞的共同特征，此前有人提出中心体扩增可以驱动遗传不稳定性，从而导致肿瘤的发生。为了验证这一假设，我们培育了果蝇品系，它们在60%的体细胞中有额外的中心体。许多有额外中心体的细胞最初形成多极纺锤体，但这些纺锤体最终变成双极。这需要有丝分裂的延迟，这是由纺锤体组装检查点(SAC)介导的。由于这种延迟，具有额外中心体的果蝇的遗传不稳定性没有显著增加，这些果蝇在许多世代中保持稳定的二倍体基因组。然而，幼虫神经干细胞的不对称分裂在额外中心体的存在下会受到影响，具有额外中心体的幼虫脑细胞在移植到野生型宿主的腹部时可能会产生转移性肿瘤。因此，中心体扩增可以启动果蝇的肿瘤发生。
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 similar to 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.