Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster
Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster
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DOI：
10.1038/ng1632
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发表时间：
2005-10-01
期刊：
影响因子：
30.8
通讯作者：
Gonzalez, C
中科院分区：
文献类型：
--
作者：
Caussinus, E;Gonzalez, C
细胞极性的丧失与癌症密切相关(1)，但因果关系的证据仍然难以捉摸。在干细胞中，极性的丧失和不对称细胞分裂的损害可能改变细胞命运，从而使子细胞无法对控制增殖的机制作出反应(2)。为了验证这一假设，我们培育了含有控制不对称细胞分裂的各种基因突变的黑腹果蝇幼虫神经母细胞，然后在移植到成年宿主后检测它们的增殖潜力。我们发现，携带raps（也称为pins）， mira， numb或pros突变的神经母细胞的幼虫脑组织增长到其初始大小的100多倍，侵入其他组织并在两周内杀死宿主。这些肿瘤变成了不朽的，可以重新移植到新的宿主体内数年。第一次植入6周后，这些肿瘤出现了基因组不稳定和中心体改变这两个恶性肿瘤的特征（3,4）。越来越多的证据表明，一些肿瘤可能是干细胞起源（5,6）。我们的研究结果表明，控制干细胞子细胞命运的几个基因中的任何一个功能的丧失都可能导致过度增殖，引发一系列事件，破坏细胞的一般意义上的稳态并导致癌症。
Loss of cell polarity and cancer are tightly correlated(1), but proof for a causative relationship has remained elusive. In stem cells, loss of polarity and impairment of asymmetric cell division could alter cell fates and thereby render daughter cells unable to respond to the mechanisms that control proliferation(2). To test this hypothesis, we generated Drosophila melanogaster larval neuroblasts containing mutations in various genes that control asymmetric cell division and then assayed their proliferative potential after transplantation into adult hosts. We found that larval brain tissue carrying neuroblasts with mutations in raps (also called pins), mira, numb or pros grew to more than 100 times their initial size, invading other tissues and killing the hosts in 2 weeks. These tumors became immortal and could be retransplanted into new hosts for years. Six weeks after the first implantation, genome instability and centrosome alterations, two traits of malignant carcinomas(3,4), appeared in these tumors. Increasing evidence suggests that some tumors may be of stem cell origin(5,6). Our results show that loss of function of any of several genes that control the fate of a stem cell's daughters may result in hyperproliferation, triggering a chain of events that subverts cell homeostasis in a general sense and leads to cancer.