LAUSR

Significance The cancer-derived cachectic factors induce wasting in the patient’s tissues, including muscle and adipose tissue. If cancers were to be equally affected by the cachectic factors, they must be wasted away. Nevertheless, cancers appear to grow during cachexia, suggesting a mechanism for protecting themselves from the cachectic factors. We employ Drosophila tumor models to demonstrate that a signaling protein Wingless works locally to protect tumors from the action of the secreted wasting factor ImpL2. Furthermore, we show that Wingless augmentation specifically in muscle could be exploited to attenuate systemic tissue wasting induced by localized tumors. Altogether, our study provides insights into the mechanism by which tumors evade the adverse effects induced by the wasting factors to avoid self-wasting. Tumors often secrete wasting factors associated with atrophy and the degeneration of host tissues. If tumors were to be 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 use Drosophila midgut tumor models to show that tumors up-regulate 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/insulin-like growth factor 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 to uphold their growth during cachexia-like wasting and implies that targeting the Wnt/Wg pathway might be an efficient treatment strategy for cancers with elevated IGFBPs.