DrosophilaAHR limits tumor growth and stem cell proliferation in the intestine

Abstract

AbstractThe aryl hydrocarbon receptor (AHR) plays important roles in intestinal homeostasis, limiting tumour growth and promoting differentiation in the intestinal epithelium. Spineless, theDrosophilahomolog of AHR, has only been studied in the context of development but not in the adult intestine. Here, we show thatspinelessis upregulated in the adult intestinal epithelium after infection withPseudomonas entomophila(P.e.). Spineless knockdown increased stem cell proliferation following infection-induced injury. Spineless overexpression limited intestinal stem cell proliferation and reduced survival after infection. In two tumour models, using eitherNotchRNAi or constitutively active Yorkie, Spineless suppressed tumour growth and doubled the lifespan of tumour-bearing flies. At the transcriptional level it reversed the gene expression changes induced in Yorkie tumours, counteracting cell proliferation and altered metabolism. These findings demonstrate a new role for Spineless in the adultDrosophilamidgut and highlight the evolutionarily conserved functions of AHR/Spineless in the control of proliferation and differentiation of the intestinal epithelium.