EyaHOST, a modular genetic system for investigation of intercellular and tumor-host interactions in Drosophila melanogaster.
| Title: | EyaHOST, a modular genetic system for investigation of intercellular and tumor-host interactions in Drosophila melanogaster. |
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| Authors: | Teles-Reis J; Center for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Jain A; Center for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Liu D; Center for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Khezri R; Center for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Antunes MG; Center for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Micheli S; Center for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Gomez AA; Center for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Dillard C; Center for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Electronic address: caroline.dillard@univ-rennes.fr.; Rusten TE; Center for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Electronic address: t.e.rusten@medisin.uio.no. |
| Source: | Cell reports methods [Cell Rep Methods] 2025 Nov 17; Vol. 5 (11), pp. 101220. Date of Electronic Publication: 2025 Nov 04. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Inc Country of Publication: United States NLM ID: 9918227360606676 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2667-2375 (Electronic) Linking ISSN: 26672375 NLM ISO Abbreviation: Cell Rep Methods Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [New York] : Elsevier Inc., [2021]- |
| MeSH Terms: | Drosophila melanogaster*/genetics ; Drosophila melanogaster*/metabolism ; Neoplasms*/pathology ; Neoplasms*/genetics ; Cell Communication*; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Animals ; Apoptosis ; Autophagy |
| Abstract: | Studying intercellular and interorgan interactions in animal models is key to understanding development, physiology, and disease. We introduce EyaHOST, a system for clonal combinatorial loss- and gain-of-function genetics in fluorescently labeled cells under QF2-QUAS eya promoter control. Distinct from mosaic analysis with a repressible cell marker (MARCM), it reserves the use of genome-wide GAL4-UAS tools to manipulate any host tissue. EyaHOST-driven RasV12 overexpression with scribble knockdown recapitulates key cancer features, including systemic catabolic switching and organ wasting. We demonstrate effective tissue-specific manipulation of host compartments, including homotypic epithelial neighbors, immune cells, fat body, and muscle. Organ-specific inhibition of autophagy or stimulation of growth signaling via PTEN knockdown in fat body or muscle prevents cachexia-like wasting. Additionally, tumors trigger caspase-driven apoptosis in the neighboring epithelium, and blocking apoptosis with p35 enhances tumor growth. EyaHOST provides a modular platform to dissect mechanisms of intercellular and interorgan communication under physiological or disease conditions.; (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of interests The authors declare no competing interests. |
| Comments: | Update of: bioRxiv. 2024 Sep 11:2024.09.06.611647. doi: 10.1101/2024.09.06.611647.. (PMID: 39314415) |
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| Contributed Indexing: | Keywords: CP: cancer biology; CP: genetics; Drosophila; QF2; Ras; Scrib; apoptosis-induced proliferation; cachexia; cancer model; cell competition; tumor-host; tumorigenesis |
| Substance Nomenclature: | 0 (Drosophila Proteins) |
| Entry Date(s): | Date Created: 20251105 Date Completed: 20251118 Latest Revision: 20251203 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12664959 |
| DOI: | 10.1016/j.crmeth.2025.101220 |
| PMID: | 41192417 |
| Database: | MEDLINE |
Journal Article