The Hippo tumor suppressor pathway triggers non-cell autonomous tumorigenesis in Drosophila

The Hippo pathway is a tumor suppressor pathway, and most related studies have indicated that its inhibition leads to tumorigenesis. However, recent studies have suggested that the activated Hippo pathway can promote tumorigenesis in certain contexts. Here, we demonstrate that the activated Hippo pathway induces non-cell-autonomous tumorigenesis, characterized by tumor markers in the Drosophila wing epithelium. This suggests that Hippo-activated cells behave similarly to "oncogenic niche cells." We find that Hippo-activated cells induce Dronc-Wingless/Spitz signaling in the hinge/ventral notum region, which causes tumorigenesis. Moreover, we identify the amino acid transporters Sat1/2, which are implicated in amino acid incorporation and function redundantly with the growth factors Wingless and Spitz to facilitate non-cell-autonomous tumorigenesis.