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. 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).

果蝇（Drosophila）的固有免疫（innate immunity）是一类机体监视系统，可感知外界刺激与细胞健康状态，并触发情境特异性应答以对抗感染、维持组织稳态。然而，固有免疫通路的不受控激活会对机体产生不利影响。在哺乳动物中，恶性细胞内的固有免疫信号通路常处于过度激活状态，进而促进肿瘤进展。果蝇肿瘤模型在促肿瘤通路互作机制的发现中发挥了重要作用，但目前对于Toll固有免疫通路（Toll innate immune pathway）是否以及如何与癌基因发生相互作用，仍知之甚少。本研究采用果蝇上皮细胞活体模型，探究Toll信号通路与致癌性Ras（Ras）之间的相互作用。我们从产卵后96小时（96 h AED, after egg deposition）的幼虫样本中提取总RNA：每个对照样本取自约50个正常眼-触角盘（eye-antennal discs, EAD），每个肿瘤样本取自约30个肿瘤眼-触角盘。我们针对4组不同样本构建了mRNA测序文库，每组均设置3次独立生物学重复：(1) 正常眼-触角盘（LacZ）；(2) 经Toll通路激活后的正常眼-触角盘（Dorsal）；(3) 肿瘤眼-触角盘（RasLacZ）；(4) 经Toll通路激活后的肿瘤眼-触角盘（RasDorsal）。