NF-κB signaling driven by oncogenic Ras contributes to tumorigenesis in a Drosophila carcinoma model.
| Title: | NF-κB signaling driven by oncogenic Ras contributes to tumorigenesis in a Drosophila carcinoma model. |
|---|---|
| Authors: | 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.; 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.; 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.; Ruiz-Duran P; 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.; Qi Y; Buck Institute for Research on Aging, Novato, California, United States of America.; Le Borgne R; Univ Rennes, CNRS-UMR, Institut de Génétique et Développement de Rennes, Rennes, France.; Jasper H; Buck Institute for Research on Aging, Novato, California, United States of America.; 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. |
| Source: | PLoS biology [PLoS Biol] 2025 Apr 28; Vol. 23 (4), pp. e3002663. Date of Electronic Publication: 2025 Apr 28 (Print Publication: 2025). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101183755 Publication Model: eCollection Cited Medium: Internet ISSN: 1545-7885 (Electronic) Linking ISSN: 15449173 NLM ISO Abbreviation: PLoS Biol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: San Francisco, CA : Public Library of Science, [2003]- |
| MeSH Terms: | NF-kappa B*/metabolism ; NF-kappa B*/genetics ; Drosophila melanogaster*/genetics ; Drosophila melanogaster*/metabolism ; Carcinogenesis*/genetics ; Carcinogenesis*/metabolism ; ras Proteins*/metabolism ; ras Proteins*/genetics ; Carcinoma*/metabolism ; Carcinoma*/pathology ; Carcinoma*/genetics ; Signal Transduction*; Drosophila Proteins/metabolism ; Drosophila Proteins/genetics ; Transcription Factors/metabolism ; Transcription Factors/genetics ; Toll-Like Receptors/metabolism ; Nuclear Proteins/metabolism ; Nuclear Proteins/genetics ; Cell Transformation, Neoplastic/genetics ; Tumor Suppressor Proteins/metabolism ; Tumor Suppressor Proteins/genetics ; Animals ; Disease Models, Animal ; DNA-Binding Proteins ; IMP Dehydrogenase ; Membrane Proteins ; Phosphoproteins |
| Abstract: | Cancer-driving mutations synergize with inflammatory stress signaling pathways during carcinogenesis. Drosophila melanogaster tumor models are increasingly recognized as models to inform conserved molecular mechanisms of tumorigenesis with both local and systemic effects of cancer. Although initial discoveries of the Toll-NFκB signaling pathway in development and immunity were pioneered in Drosophila, limited information is available for its role in cancer progression. Using a well-studied cooperative RasV12-driven epithelial-derived tumor model, we here describe functions of Toll-NF-κB signaling in malignant RasV12, scrib- tumors. The extracellular Toll pathway components ModSP and PGRP-SA and intracellular signaling Kinase, Pelle/IRAK, are rate-limiting for tumor growth. The Toll pathway NFκB protein Dorsal as well as cactus/IκΒ show elevated expression in tumors with highest expression in invasive cell populations. Oncogenic RasV12, and not loss of scribble, confers increased expression and heterogenous distribution of two Dorsal isoforms, DorsalA and DorsalB, in different tumor cell populations. Mechanistic analyses demonstrates that Dorsal, in concert with the BTB-transcription factor Chinmo, drives growth and malignancy by suppressing differentiation, counteracting apoptosis, and promoting invasion of RasV12, scrib- tumors.; (Copyright: © 2025 Dillard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.) |
| Competing Interests: | The authors have declared that no competing interests exist. |
| Comments: | Comment in: PLoS Biol. 2025 Apr 29;23(4):e3003088. doi: 10.1371/journal.pbio.3003088.. (PMID: 40300148) |
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| Substance Nomenclature: | 0 (Drosophila Proteins); 0 (NF-kappa B); 0 (Scrib protein, Drosophila); EC 3.6.5.2 (ras Proteins); 0 (Transcription Factors); 0 (Toll-Like Receptors); 0 (Nuclear Proteins); 149059-01-8 (cact protein, Drosophila); 0 (Tumor Suppressor Proteins); EC 1.1.1.205 (ras protein, Drosophila); 0 (DNA-Binding Proteins); EC 1.1.1.205 (IMP Dehydrogenase); 0 (Membrane Proteins); 0 (Phosphoproteins) |
| Entry Date(s): | Date Created: 20250428 Date Completed: 20250428 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12037074 |
| DOI: | 10.1371/journal.pbio.3002663 |
| PMID: | 40294135 |
| Database: | MEDLINE |
Journal Article