Hippo-activated cells induce non-cell autonomous tumorigenesis in Drosophila

The Hippo pathway is known as a tumor-suppressor pathway, and most related studies have indicated that the inhibition of the Hippo pathway leads to tumorigenesis. However, recent studies have suggested that the activated Hippo pathway can potentially promote tumorigenesis in some contexts. Here, we show that the activated Hippo pathway induces non-cell-autonomous tumorigenesis characterized by tumor markers in the Drosophila wing epithelium. This suggests that the Hippo-activated cells behave similarly to "oncogenic niche cells." We found that the Hippo-activated cells distantly induced tumor-like cells exhibiting aberrant cell proliferation. Moreover, we identified the evolutionarily conserved amino acid transporters, Sat1/2, that redundantly work with the growth factors, Wingless and Spitz, for non-cell autonomous tumorigenesis. Our findings provide novel insights into the Hippo pathway and may be useful in developing cancer treatments targeting the Hippo pathway.