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营养限制增强了有丝分裂组织中缺乏肿瘤抑制因子PTEN的细胞的增殖潜力。

Nutrient restriction enhances the proliferative potential of cells lacking the tumor suppressor PTEN in mitotic tissues.

作者信息

Nowak Katarzyna, Seisenbacher Gerhard, Hafen Ernst, Stocker Hugo

机构信息

Institute of Molecular Systems Biology , ETH Zürich , Zürich , Switzerland.

出版信息

Elife. 2013 Jul 9;2:e00380. doi: 10.7554/eLife.00380.

Abstract

How single cells in a mitotic tissue progressively acquire hallmarks of cancer is poorly understood. We exploited mitotic recombination in developing Drosophila imaginal tissues to analyze the behavior of cells devoid of the tumor suppressor PTEN, a negative regulator of PI3K signaling, under varying nutritional conditions. Cells lacking PTEN strongly overproliferated specifically in nutrient restricted larvae. Although the PTEN mutant cells were sensitive to starvation, they successfully competed with neighboring cells by autonomous and non-autonomous mechanisms distinct from cell competition. The overgrowth was strictly dependent on the activity of the downstream components Akt/PKB and TORC1, and a reduction in amino acid uptake by reducing the levels of the amino acid transporter Slimfast caused clones of PTEN mutant cells to collapse. Our findings demonstrate how limiting nutritional conditions impact on cells lacking the tumor suppressor PTEN to cause hyperplastic overgrowth. DOI:http://dx.doi.org/10.7554/eLife.00380.001.

摘要

有丝分裂组织中的单个细胞如何逐渐获得癌症特征,目前尚不清楚。我们利用发育中的果蝇成虫组织中的有丝分裂重组,来分析在不同营养条件下缺乏肿瘤抑制因子PTEN(PI3K信号的负调节因子)的细胞的行为。缺乏PTEN的细胞在营养受限的幼虫中特别强烈地过度增殖。尽管PTEN突变细胞对饥饿敏感,但它们通过与细胞竞争不同的自主和非自主机制成功地与邻近细胞竞争。过度生长严格依赖于下游成分Akt/PKB和TORC1的活性,并且通过降低氨基酸转运蛋白Slimfast的水平来减少氨基酸摄取,会导致PTEN突变细胞克隆崩溃。我们的研究结果表明,有限的营养条件如何影响缺乏肿瘤抑制因子PTEN的细胞,从而导致增生性过度生长。DOI:http://dx.doi.org/10.7554/eLife.00380.001

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9163/3707060/a6f6009031dc/elife00380f001.jpg

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