Yorkie and JNK Control Tumorigenesis in Drosophila Cells with Cytokinesis Failure
Yorkie and JNK Control Tumorigenesis in Drosophila Cells with Cytokinesis Failure
复制标题
DOI：
10.1016/j.celrep.2018.04.006
复制
发表时间：
2018-05-01
期刊：
影响因子：
8.8
通讯作者：
Herranz, Hector
中科院分区：
文献类型：
--
作者：
Gerlach, Stephan U.;Eichenlaub, Teresa;Herranz, Hector
胞质分裂失败可导致多倍体细胞的形成，随后的有丝分裂可导致非整倍体和肿瘤形成。已经描述了限制这些细胞的致癌潜力的肿瘤抑制机制。然而，这些肿瘤抑制屏障的普遍适用性仍然存在争议。在这里，我们使用果蝇上皮细胞来研究胞质分裂失败在体内的后果。我们报告说，裂解缺陷触发激活JNK通路，导致下调的抑制剂凋亡DIAP 1和程序性细胞死亡。Yorkie克服了JNK的肿瘤抑制作用并诱导肿瘤形成。Yorkie调节细胞周期磷酸酶Cdc 25/string，其在胞质分裂失败的背景下驱动肿瘤发生。这些结果突出了JNK途径在具有缺陷胞质分裂的上皮细胞中的功能意义，并阐明了新兴肿瘤细胞绕过这种肿瘤抑制屏障并发展成肿瘤的机制。
Cytokinesis failure may result in the formation of polyploid cells, and subsequent mitosis can lead to aneuploidy and tumor formation. Tumor suppressor mechanisms limiting the oncogenic potential of these cells have been described. However, the universal applicability of these tumor-suppressive barriers remains controversial. Here, we use Drosophila epithelial cells to investigate the consequences of cytokinesis failure in vivo. We report that cleavage defects trigger the activation of the JNK pathway, leading to downregulation of the inhibitor of apoptosis DIAP1 and programmed cell death. Yorkie overcomes the tumor-suppressive role of JNK and induces neoplasia. Yorkie regulates the cell cycle phosphatase Cdc25/string, which drives tumorigenesis in a context of cytokinesis failure. These results highlight the functional significance of the JNK pathway in epithelial cells with defective cytokinesis and elucidate a mechanism used by emerging tumor cells to bypass this tumor-suppressive barrier and develop into tumors.