Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster
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- 4 September 2005
- journal article
- research article
- Published by Springer Nature in Nature Genetics
- Vol. 37 (10) , 1125-1129
- https://doi.org/10.1038/ng1632
Abstract
Loss of cell polarity and cancer are tightly correlated1, 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 proliferation2. 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 carcinomas3,4, appeared in these tumors. Increasing evidence suggests that some tumors may be of stem cell origin5,6. 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.Keywords
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