RRC ID 67567
Author Ding G, Xiang X, Hu Y, Xiao G, Chen Y, Binari R, Comjean A, Li J, Rushworth E, Fu Z, Mohr SE, Perrimon N, Song W.
Title Coordination of tumor growth and host wasting by tumor-derived Upd3.
Journal Cell Rep
Abstract 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.
Volume 36(7)
Pages 109553
Published 2021-8-17
DOI 10.1016/j.celrep.2021.109553
PII S2211-1247(21)00987-6
PMID 34407411
PMC PMC8410949
MeSH Animals Cell Proliferation Drosophila Proteins / metabolism* Drosophila melanogaster / cytology* Drosophila melanogaster / metabolism* Fat Body / metabolism Homeostasis Insulin / metabolism Intestines / cytology Janus Kinases / metabolism Lipid Metabolism Mitochondria / metabolism Mitochondria / ultrastructure Muscles / physiopathology Neoplasms / metabolism* Neoplasms / pathology* STAT Transcription Factors / metabolism Signal Transduction Stem Cells / metabolism
IF 8.109
Drosophila 15009R-3