title: Transformed epithelia trigger non-tissue-autonomous tumor suppressor response by adipocytes via activation of Toll and Eiger/TNF signaling.
abstract: High tumor burden is associated with increased levels of circulating inflammatory cytokines that influence the pathophysiology of the tumor and its environment. The cellular and molecular events mediating the organismal response to a growing tumor are poorly understood. Here, we report a bidirectional crosstalk between epithelial tumors and the fat body-a peripheral immune tissue-in Drosophila. Tumors trigger a systemic immune response through activation of Eiger/TNF signaling, which leads to Toll pathway upregulation in adipocytes. Reciprocally, Toll elicits a non-tissue-autonomous program in adipocytes, which drives tumor cell death. Hemocytes play a critical role in this system by producing the ligands Spätzle and Eiger, which are required for Toll activation in the fat body and tumor cell death. Altogether, our results provide a paradigm for a long-range tumor suppression function of adipocytes in Drosophila, which may represent an evolutionarily conserved mechanism in the organismal response to solid tumors.
authors.affiliation: The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Federica
authors.initials: F
authors.lastname: Parisi
authors.affiliation: The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Rhoda K
authors.initials: RK
authors.lastname: Stefanatos
authors.affiliation: The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Strathdee
authors.affiliation: The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Yachuan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK. Electronic address: m.vidal@beatson.gla.ac.uk.
authors.forename: Marcos
authors.initials: M
authors.lastname: Vidal
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D063646:Carcinogenesis / Q000378:metabolism; D048708:Cell Growth Processes / Q000502:physiology; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D005260:Female; D006434:Hemocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C464573:egr protein, Drosophila