Tumors Negate the Action of ImpL2 by Elevating Wingless

Summary Tumors often secrete wasting factors associated with atrophy and degeneration of host tissues. If tumors were affected by the wasting factors, mechanisms allowing tumors to evade the adverse effects of the wasting factors must exist and impairing such mechanisms may attenuate tumors. We used Drosophila midgut tumor models to show that tumors upregulate Wingless (Wg) to oppose the growth-impeding effects caused by the wasting factor, ImpL2 (Insulin-like growth factor binding protein (IGFBP)-related protein). Growth of Yorkie (Yki)-induced tumors is dependent on Wg while either elimination of ImpL2 or elevation of Insulin/IGF signaling in tumors revokes this dependency. Notably, Wg augmentation could be a general mechanism for supporting the growth of tumors with elevated ImpL2 and exploited to attenuate muscle degeneration during wasting. Our study elucidates the mechanism by which tumors negate the action of ImpL2 and implies that targeting the Wnt/Wg pathway might be an efficient treatment strategy for cancers with elevated IGFBPs.