Macrophages facilitate subclonalcooperation-induced tumor malignancy by hijacking the innate immune system

By applying mosaic analysis with a repressible cell marker (MACRM) system in Drosophila larva eye-antennal disc, we succeeded to establish an intercellular communication mediated epithelial tumor model, where we found the ablation of Drosophila tricellular junction protein M6 in WT cells can stimulate surrounding cells bearing oncogenic RasV12 to transition from benign to malignant tumors through intercellular communication. In order to illustrate molecular mechanisms underlying, we harvested both benign tumors (RasV12//WT) and maligant tumors (RasV12//M6-/-) were subjected to bulk RNA-seq, which indicated that Toll and Imd signaling pathway plays a vital role in the regulation of RasV12//M6-/- tumor. In combination with scRNA-seq data analysis of wildtype eye-antennal discs (WT) and maligant tumors (RasV12//M6-/-), and experiments validation, we found RasV12//M6-/- tumors were regulated by Drosophila macrophages and epithelial cells via Toll and Imd signaling pathway, MAPK signlaing pathway, and Hippo signaling pathway.