Tsai, M., Sun, J., Alexandre, C., Shapiro, M., Franchet, A., Li, Y., Gould, A.P., Vincent, J.P., Stockinger, B., Diny, N.L. (2025). Drosophila AHR limits tumor growth and stem cell proliferation in the intestine.  Wellcome Open Res. 10(): 38.

FBrf0262106

Research paper

The transcription factor aryl hydrocarbon receptor (AHR) plays important roles in the intestine, limiting tumour growth and promoting the normal epithelial lining. Spineless, the fruit fly homolog of AHR, has only been studied in the context of embryonic development but not in the intestine of adult flies. Here, we show that spineless is upregulated in the adult intestinal epithelium after infection with a bacterium. Blocking Spineless function increased stem cell proliferation after bacterial infection. Increasing Spineless had the opposite effect and limited intestinal stem cell proliferation. It also reduced survival after bacterial infection. In two separate tumour models, Spineless suppressed tumour growth and doubled the lifespan of tumour-bearing flies. Increasing Spineless reversed the gene expression changes induced in tumours, counteracting cell proliferation and changes to the cellular metabolism. These findings demonstrate a new role for Spineless in the adult fruit fly midgut and highlight the evolutionarily conserved functions of mammalian AHR and fruit fly Spineless in the control of proliferation and differentiation of the intestinal epithelium.

PMC11982807 (PMC) (EuropePMC)