Tumors overcome the action of the wasting factor ImpL2 by locally elevating Wnt/Wingless.
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.
['Lee|Jiae|J|0000-0001-5898-5728', 'Ng|Katelyn G-L|KG|0000-0001-9282-6261', 'Dombek|Kenneth M|KM|0000-0002-6941-4063', 'Eom|Dae Seok|DS|0000-0002-0617-8788', 'Kwon|Young V|YV|0000-0002-8937-3182']
D000818:Animals D029721:Drosophila Proteins D004331:Drosophila melanogaster D018969:Insulin-Like Growth Factor Binding Proteins D009363:Neoplasm Proteins D009374:Neoplasms, Experimental D060449:Wnt Signaling Pathway D051155:Wnt1 Protein
tumor ImpL2 Wnt Yorkie cachexia