Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
Development. 2012 Nov;139(21):4051-61. doi: 10.1242/dev.076760. Epub 2012 Sep 19.
Cell competition is a conserved mechanism that regulates organ size and shares properties with the early stages of cancer. In Drosophila, wing cells with increased Myc or with optimum ribosome function become supercompetitors that kill their wild-type neighbors (called losers) up to several cell diameters away. Here, we report that modulating STAT activity levels regulates competitor status. Cells lacking STAT become losers that are killed by neighboring wild-type cells. By contrast, cells with hyper-activated STAT become supercompetitors that kill losers located at a distance in a manner that is dependent on hid but independent of Myc, Yorkie, Wingless signaling, and of ribosome biogenesis. These results indicate that STAT, Wingless and Myc are major parallel regulators of cell competition, which may converge on signals that non-autonomously kill losers. As hyper-activated STATs are causal to tumorigenesis and stem cell niche occupancy, our results have therapeutic implications for cancer and regenerative medicine.
细胞竞争是一种保守的机制，可调节器官大小，并与癌症的早期阶段具有共同的特性。在果蝇中，Myc 增加或核糖体功能最佳的翅膀细胞成为超级竞争者，可杀死其野生型邻居（称为失败者），距离可达几个细胞直径。在这里，我们报告说，调节 STAT 活性水平可调节竞争者状态。缺乏 STAT 的细胞成为失败者，会被邻近的野生型细胞杀死。相比之下，具有超激活 STAT 的细胞成为超级竞争者，可杀死远处的失败者，这种方式依赖于 hid，但独立于 Myc、Wingless 信号和核糖体生物发生。这些结果表明，STAT、Wingless 和 Myc 是细胞竞争的主要平行调节剂，它们可能集中在非自主杀死失败者的信号上。由于超激活的 STATs 是肿瘤发生和干细胞生态位占据的原因，我们的结果对癌症和再生医学具有治疗意义。
