Maintenance of renal function and fluid transport are essential for vertebrates and invertebrates to adapt to physiological and pathological challenges. Human patients with malignant tumours frequently develop detrimental renal dysfunction and oliguria, and previous studies suggest the involvement of chemotherapeutic toxicity and tumour-associated inflammation1,2. However, how tumours might directly modulate renal functions remains largely unclear. Here, using conserved tumour models in Drosophila melanogaster3, we characterized isoform F of ion transport peptide (ITPF) as a fly antidiuretic hormone that is secreted by a subset of yki3SA gut tumour cells, impairs renal function and causes severe abdomen bloating and fluid accumulation. Mechanistically, tumour-derived ITPF targets the G-protein-coupled receptor TkR99D in stellate cells of Malpighian tubules—an excretory organ that is equivalent to renal tubules4—to activate nitric oxide synthase–cGMP signalling and inh
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1118. (
B) Heatmap of the expression of TSC genes averaged across 2 days of observation. The presence of the characteristic circadian patterns in the tissue is indicated with black rectangles around the heatmaps. The number at the left designates the number of detected TSC genes. (
C and
D) Heatmap of cycling in two (C) and three tissues (D) gene expression averaged across 2 days of observation. Black rectangles indicate tissues in which genes were found to be cycling. For (B) to (D), lighter areas or the heatmaps correspond to lower expression levels. The time is indicated at the bottom of the heatmap. (