A Novel Drosophila Model of Cancer Cachexia Reveals Conserved Jak/Stat Dependent Glucagon-like Akh Activation as a Driver of Metabolic Reprogramming and Systemic Wasting
Yu, K.; Moroak, G. S.; Verheyen, E.
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Cancer-associated cachexia is a systemic wasting syndrome with no effective therapies, and results in millions of deaths annually. Here, we establish a novel Drosophila model of cancer cachexia using overexpression of Hipk and constitutively active Sik3 in larval epithelial tissue. Tumor-bearing larvae has significant muscle and fat body wasting, together with elevated carbohydrates and lipolysis. Mechanistically, tumors secrete Unpaired ligands that activate Jak/Stat signaling in corpora cardiaca (cc) cells, inducing the expression and protein levels of glucagon-like hormone Adipokinetic hormone (Akh). Elevated Akh, together with the lipase Brummer (Bmm), drives the aforementioned systemic metabolic reprogramming and tissue catabolism. In conclusion, this study identifies a conserved tumor-host Upd-JAK/STAT-Akh signaling axis that contributes to organ wasting.
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