Tumour-derived Ilp8 and Upd3 control intestinal progenitor cells depletion during cachexia in Drosophila larvae

In animals, tumour development triggers systemic effects, impacting the physiology of distant organs. In Drosophila larvae, wing disc neoplastic tumours 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 tumours 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 disorganisation of the niche cells which enter precocious differentiation. Importantly, these intestinal cell type alterations are initiated before the onset of reduced food intake, and of muscle and adipose tissue atrophies, and thus represent a new paraneoplastic phenotype. Screening for mediators, we show that tumour derived Ilp8 and Upd3 control AMPs number and niche specification respectively. ### Competing Interest Statement The authors have declared no competing interest. French Ministry for Education Research and Technology, , La Ligue Contre le Cancer, , Fondation ARC pour la Recherche sur le Cancer, , PJA20181207757, ARCPJA2023080007002 GSO-Emergence, , Agence Nationale de la Recherche, , ANR-18-CE14-0041 SIRIC Montpellier Cancer, , INCa-DGOS-INSERM-ITMO Cancer_18004