IRCM, Inserm, University of Montpellier, ICM, Montpellier, France.
IRCM, Inserm, University of Montpellier, ICM, CNRS, Montpellier, France.
Development. 2022 Feb 1;149(3). doi: 10.1242/dev.200110. Epub 2022 Feb 3.
Aggressive neoplastic growth can be initiated by a limited number of genetic alterations, such as the well-established cooperation between loss of cell architecture and hyperactive signaling pathways. However, our understanding of how these different alterations interact and influence each other remains very incomplete. Using Drosophila paradigms of imaginal wing disc epithelial growth, we have monitored the changes in Notch pathway activity according to the polarity status of cells (scrib mutant). We show that the scrib mutation impacts the direct transcriptional output of the Notch pathway, without altering the global distribution of Su(H), the Notch-dedicated transcription factor. The Notch-dependent neoplasms require, however, the action of a group of transcription factors, similar to those previously identified for Ras/scrib neoplasm (namely AP-1, Stat92E, Ftz-F1 and basic leucine zipper factors), further suggesting the importance of this transcription factor network during neoplastic growth. Finally, our work highlights some Notch/scrib specificities, in particular the role of the PAR domain-containing basic leucine zipper transcription factor and Notch direct target Pdp1 for neoplastic growth.
肿瘤的侵袭性生长可能由少数遗传改变引发，例如细胞结构丧失和信号通路过度激活之间已经确立的合作关系。然而，我们对这些不同改变如何相互作用和影响彼此的理解还非常不完整。利用果蝇胚胎翅膀外胚层组织生长的范例，我们根据细胞极性状态（scrib 突变体）监测 Notch 通路活性的变化。我们表明 scrib 突变影响 Notch 通路的直接转录输出，而不改变 Notch 专用转录因子 Su(H)的整体分布。然而，Notch 依赖性肿瘤需要一组转录因子的作用，类似于先前鉴定的 Ras/scrib 肿瘤（即 AP-1、Stat92E、Ftz-F1 和碱性亮氨酸拉链因子），这进一步表明在肿瘤生长过程中这个转录因子网络的重要性。最后，我们的工作强调了一些 Notch/scrib 的特异性，特别是含有 PAR 结构域的碱性亮氨酸拉链转录因子和 Notch 直接靶标 Pdp1 在肿瘤生长中的作用。
