Coordination of tumor growth and host wasting by tumor-derived Upd3.

Guangming Ding, Xiaoxiang Xiang, Yanhui Hu, Gen Xiao, Yuchen Chen, Richard Binari, Aram Comjean, Jiaying Li, Elisabeth Rushworth, Zhenming Fu, Stephanie E Mohr, Norbert Perrimon, Wei Song

Cell reports 2021 Aug 17

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yki-induced gut tumors in Drosophila are associated with host wasting, including muscle dysfunction, lipid loss, and hyperglycemia, a condition reminiscent of human cancer cachexia. We previously used this model to identify tumor-derived ligands that contribute to host wasting. To identify additional molecular networks involved in host-tumor interactions, we develop PathON, a web-based tool analyzing the major signaling pathways in Drosophila, and uncover the Upd3/Jak/Stat axis as an important modulator. We find that yki-gut tumors secrete Upd3 to promote self-overproliferation and enhance Jak/Stat signaling in host organs to cause wasting, including muscle dysfunction, lipid loss, and hyperglycemia. We further reveal that Upd3/Jak/Stat signaling in the host organs directly triggers the expression of ImpL2, an antagonistic binding protein for insulin-like peptides, to impair insulin signaling and energy balance. Altogether, our results demonstrate that yki-gut tumors produce a Jak/Stat pathway ligand, Upd3, that regulates both self-growth and host wasting. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Guangming Ding, Xiaoxiang Xiang, Yanhui Hu, Gen Xiao, Yuchen Chen, Richard Binari, Aram Comjean, Jiaying Li, Elisabeth Rushworth, Zhenming Fu, Stephanie E Mohr, Norbert Perrimon, Wei Song. Coordination of tumor growth and host wasting by tumor-derived Upd3. Cell reports. 2021 Aug 17;36(7):109553