Activation of the innate immune system accelerates growth in cooperation with oncogenic Ras.. Activation of the innate immune system accelerates growth in cooperation with oncogenic Ras.

Innate immunity in Drosophila acts as an organismal surveillance system that measures external stimuli or cellular fitness and triggers context-specific responses to fight infections and maintain tissue homeostasis. However, uncontrolled activation of innate immune pathways can be detrimental to the system. In mammals, innate immune signaling is often overactivated in malignant cells and contributes to tumor progression. Drosophila tumor models have been instrumental in the discovery of interactions between pathways that promote tumorigenesis, but little is known about whether and how the Toll innate immune pathway interacts with oncogenes. Here we use a Drosophila epithelial in vivo model to investigate the interplay between Toll signaling and oncogenic Ras. Overall design: Total RNA was extracted from approximately 50 control or 30 tumor eye-antennal discs (EAD) per sample from larvae at 96 h AED (after egg deposition). We generated mRNA sequencing libraries from four different samples, each in biologically independent triplicates: (1) Control EADs (LacZ), (2) Control EADs after Toll pathway activation (Dorsal), (3) Tumor EADs (RasLacZ) and (4) Tumor EADs after Toll pathway activation (RasDorsal).

先天免疫（innate immunity）是果蝇（Drosophila）的机体监视系统，可感知外界刺激或细胞健康状态，并触发特定情境下的应答以抵御感染、维持组织稳态（tissue homeostasis）。然而，先天免疫通路的过度激活会对机体造成有害影响。在哺乳动物（mammals）中，恶性细胞内的先天免疫信号通路常过度激活，进而促进肿瘤进展（tumor progression）。果蝇肿瘤模型（Drosophila tumor models）在揭示促肿瘤发生通路间的相互作用方面发挥了关键作用，但目前对于Toll先天免疫通路（Toll innate immune pathway）是否以及如何与癌基因（oncogene）发生相互作用，仍不甚明晰。本文采用果蝇上皮细胞体内模型（Drosophila epithelial in vivo model），探究Toll信号通路（Toll signaling）与致癌性Ras（oncogenic Ras）之间的相互作用。

实验设计概述：我们从产卵后96小时（96 h AED, after egg deposition）的幼虫样本中，每份样本提取约50个对照眼-触角盘（eye-antennal discs, 简称EAD）或30个肿瘤性眼-触角盘的总RNA。我们针对4组不同样本构建了mRNA测序文库，每组均设置3次生物学重复：
（1）对照眼-触角盘（LacZ）；
（2）Toll通路激活后的对照眼-触角盘（Dorsal）；
（3）肿瘤性眼-触角盘（RasLacZ）；
（4）Toll通路激活后的肿瘤性眼-触角盘（RasDorsal）。