ABSTRACTCommunication between neoplastic cells and cells of their microenvironment is critical to cancer progression. To investigate the role of cytoneme-mediated signaling as a mechanism for distributing growth factor signaling proteins between tumor and tumor-associated cells, we analyzed EGFR and RET Drosophila tumor models. We tested several genetic loss-of-function conditions that impair cytoneme-mediated signaling.diaphanous, Neuroglian, SCAR, capriciousare genes that cytonemes require during normal development. Genetic inhibition of cytonemes restored apical basal polarity to tumor cells, reduced tumor growth, and increased organism survival. These findings suggest that cytonemes traffic the signaling proteins that move between tumor and stromal cells, and that cytoneme-mediated signaling is required for tumor growth and malignancy.SummaryEssential cytonemes for paracrine signaling in Drosophila tumors