Work

A Drosophila tumor model identifies a conserved Upd–JAK/STAT–Akh signaling axis associated with metabolic changes in cancer cachexia

Year: 2026

Type: article

Abstract: Cancer-associated cachexia is a systemic wasting syndrome with no effective therapies, and it results in millions of deaths annually. Here, we established a Drosophila model of cancer cachexia using overexpression of Hipk and constitutively active Sik3 in larval epithelial tissue. Tumor-bearing larvae had significant muscle and fat body wasting, together with elevated carbohydrates and lipolysis. Mechanistically, tumors secrete Unpaired (Upd) ligands that activate JAK/STAT signaling in corpora cardiaca cells, inducing the expression of glucagon-like hormone Adipokinetic hormone (Akh). Elevated Akh, together with the lipase Brummer (Bmm), drives this 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.

Source: Disease Models & Mechanisms

DOI: 10.1242/dmm.052659

Authors: Kewei Yu, Gurpreet S. Moroak, Esther M. Verheyen

Institution: Simon Fraser University

Language: English

Topic: Muscle Physiology and Disorders

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,750