Tumor-derived Ilp8 and Upd3 contribute to intestinal progenitor cells depletion during cachexia in Drosophila larvae

In animals, tumor development triggers systemic effects, impacting the physiology of distant organs. In Drosophila larvae, wing disc neoplastic tumors result in developmental delay and organ wasting reminiscent of cachexia. This paraneoplastic syndrome affects many organs, but its effects on the intestine, a key organ in the regulation of nutrient and energy homeostasis, remain understudied. We describe here that neoplastic tumors also affect the development of the larval midgut, leading to altered cell-type numbers, with a depletion of the stem-cell-like adult midgut precursors (AMPs), and a disorganization of the niche cells which enter precocious differentiation. Importantly, these intestinal cell type alterations are initiated before the onset of muscle and adipose tissue atrophies, and thus represent a new paraneoplastic phenotype. Screening for mediators, we show that tumor-derived Ilp8 and Upd3 contribute to AMP numbers and niche specification, respectively.