Fig. 3: Paraneoplastic effects of fly tumors.

Endocrine signals from tumors cause pathologies in distant organs. Some effects have been demonstrated in larvae and others in the adult; see text for details. Tumor-associated macrophages secrete Spz, which activates Toll signaling in the fat body to trigger production of the antimicrobial peptide Defensin (a). Defensin, working along with macrophage-produced Egr/TNF, binds to and kills tumor cells. ImpL2/IGFBP induces systemic insulin resistance, leading to cachexia-like wasting and degeneration of fat body (b) and muscle (c). Reception of tumor-produced Pvf/VEGF in adult fat body and muscle, and Bnl/FGF in larval muscle, also induces wasting. Wasting muscles supply amino acids via autophagy (d) that are taken up by the tumor and promote tumor growth. Ilp8/INSL3 acts on brain neurons to inhibit the production and release of pupation-promoting hormones in the larvae; it also acts in the adult to stimulate brain production of anorexigenic peptides (e). Unknown tumor-dependent factors cause the host to retain excess fluids; this may be due to actions on the malpighian tubules (f). Some combination of these pathologies, along with other currently unrecognized effects, kills hosts prematurely (g).

Figures 1, 2, and 3 were drawn by Nature Reviews Cancer art editor, not the authors of the paper. They can be found in the published version of the paper at DOI: 10.1038/s41568-021-00387-5.