qRT-PCR primers used in this study.

Innate immunity in Drosophila acts as an organismal surveillance system for 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. 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. In the absence of oncogenic Ras (RasV12), Toll signaling suppresses differentiation and induces apoptosis. In contrast, in the context of RasV12, cells are protected from cell death and Dorsal promotes cell survival and proliferation to drive hyperplasia. Taken together, we show that the tissue-protective functions of innate immune activity can be hijacked by pre-malignant cells to induce tumorous overgrowth.

果蝇固有免疫（innate immunity）作为机体的监视系统，可感知外界刺激与细胞状态，触发特定情境下的应答以对抗感染并维持组织稳态。然而，固有免疫通路的异常激活会产生有害影响。在哺乳动物中，固有免疫信号常在恶性细胞中过度激活，并推动肿瘤进展。果蝇肿瘤模型在促肿瘤通路间相互作用的相关研究中发挥了关键作用，但目前对于Toll固有免疫通路（Toll innate immune pathway）是否以及如何与致癌基因（oncogenes）发生相互作用，仍所知有限。本研究借助果蝇上皮细胞体内模型，探究Toll信号通路与致癌性Ras之间的相互调控关系。在未表达致癌性Ras（RasV12）的情况下，Toll信号通路会抑制细胞分化并诱导细胞凋亡（apoptosis）。与之相反，在表达RasV12的情境中，细胞可免受细胞死亡的威胁，且背蛋白（Dorsal）会促进细胞存活与增殖，进而引发组织增生（hyperplasia）。综上，本研究证实，固有免疫活性的组织保护功能可被癌前细胞（pre-malignant cells）劫持，从而诱导肿瘤性过度增殖。