一个特定于瘤的分子网络通过强制执行JNK-YKI料循环来促进Drosophila的瘤生长
bioRxiv : the preprint server for biology
|October 31, 2023
概括
在Drosophila中Ras瘤基因的激活触发了一个新的无翼-Dronc-JNK-Yki信号网络,通过破坏细胞极性和促进癌症特征来驱动瘤生长.
科学领域:
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
- 在瘤学瘤学.
背景情况:
- 癌细胞通过改变细胞间和信号相互作用来获得癌症的标志.
- 细胞极性受损和激活的瘤基因,如Jun N-终端激酶 (JNK) 和Yorkie (Yki),促进癌症特征,如入侵和持续增殖.
- JNK,Yki及其下游因素被认为是通过亲瘤信号和细胞竞争驱动瘤生长的驱动因素.
研究的目的:
- 阐明在瘤细胞中汇聚JNK和Yki的信号,这些信号有助于获得癌症特征.
- 通过Ras激活来识别参与瘤发生的新型分子网络.
主要方法:
- 在Drosophila melanogaster中利用合作性瘤发生的马赛克模型.
- 研究了无翼 (Wg),Dronc,JNK和Yki信号通路在Ras驱动的瘤生长中的作用.
- 研究了Wg-Dronc-Yki-JNK网络在极性受损细胞和正常细胞中的激活.
主要成果:
- 拉斯瘤细胞在Wg,Dronc,JNK和Yki途径中显示出增加的信号,所有这些都对瘤生长至关重要.
- 发现了一个以前未知的网络,涉及Wg,Dronc,JNK和Yki,驱动Ras瘤扩张.
- 证明Wg和Dronc在JNK-Yki正反循环上融合,放大了瘤生长的信号.
- 观察到Wg-Dronc-Yki-JNK网络的特定激活,仅在极性受损的瘤细胞中.
结论:
- Wg-Dronc-Yki-JNK分子网络是Ras激活的Drosophila模型中瘤生长的关键驱动因素.
- 这种网络在瘤细胞中特别被激活,瘤细胞的顶-基底极性受损.
- 了解这些分子网络为信号通路的改变和促进瘤发生的矛盾信号提供了洞察力.
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