Centrosome dysfunction in Drosophila neural stem cells causes tumors that are not due to genome instability
Centrosome dysfunction in Drosophila neural stem cells causes tumors that are not due to genome instability
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DOI：
10.1016/j.cub.2008.07.029
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发表时间：
2008-08-26
期刊：
影响因子：
9.2
通讯作者：
Gonzalez, Cayetano
中科院分区：
文献类型：
--
作者：
Castellanos, Elisabeth;Dominguez, Paloma;Gonzalez, Cayetano
基因组不稳定性（GI）和中心体改变是人类癌症的常见特征[1，2]。人们怀疑中心体功能障碍可能通过引起GI而引起肿瘤，但目前仍缺乏直接的实验证据[3]。为了探索中心体功能和过度生长之间可能的功能联系，我们分析了一系列影响果蝇中不同中心体蛋白的突变体的致瘤潜力。我们已经发现，一个显着的数量这样的突变条件是致瘤性的幼虫脑组织中，自我更新的不对称分裂的神经干细胞是频繁的，但不是在对称分裂的上皮细胞。我们还发现，在我们的试验中，增加GI而不引起中心体功能障碍的突变不会致瘤。从这些观察结果中，我们得出结论，中心体功能障碍引起的肿瘤不能仅仅用由此产生的基因组不稳定性来解释。我们认为这种肿瘤可能是由神经干细胞的不对称分裂受损引起的[4]。这些结果表明，中心体丢失远非无害，而是苍蝇的一种潜在危险。
Genome instability (GI) and centrosomal alterations are common traits in human cancer [1, 2]. it is suspected that centrosome dysfunction may cause tumors by bringing about GI, but direct experimental proof is still lacking [3]. To explore the possible functional link between centrosome function and overgrowth, we have assayed the tumorigenic potential of a series of mutants that affect different centrosomal proteins in Drosophila. We have found that a significant number of such mutant conditions are tumorigenic in larval brain tissue, where self-renewing asymmetric division of neural stem cells is frequent, but not in symmetrically dividing epithelial cells. We have also found that mutations that increase GI without causing centrosome dysfunction are not tumorigenic in our assay. From these observations, we conclude that the tumors caused by centrosome dysfunction cannot be explained solely by the resulting genome instability. We propose that such tumors might be caused by impaired asymmetric division of neural stem cells [4]. These results show that centrosome loss, far from being innocuous, is a potentially dangerous condition in flies.