| Title: |
NF-κB signaling driven by oncogenic Ras contributes to tumorigenesis in a Drosophila carcinoma model |
| Authors: |
Dillard, Caroline; Teles-Reis, José; Jain, Ashish; Gonçalves Antunes, Marina; Ruiz-Duran, Paula; Qi, Yanyan; Le Borgne, Roland; Jasper, Heinrich; Rusten, Tor, Erik |
| Contributors: |
Oslo University Hospital Oslo; Buck Institute for Research on Aging; Institut de Génétique et Développement de Rennes (IGDR); Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes (Biosit : Biologie - Santé - Innovation Technologique); University of Oslo (UiO); RLB was financed by the French National Research Agency (ANR-20-CE13-0015). CD, JTR, AJ, PRD, and TER were financed by The Norwegian Research Council (https://www.forskningsradet.no/) and Toppforsk and Center of Excellence (CanCell) grants #262652 and #276070. MGA is supported by grant #247130 from The Norwegian Cancer Society (https://kreftforeningen.no/) awarded to TER.; We thank Drs. Steven A. Wasserman and Amy Kieger, Bruno Lemaitre, Claude Desplan, the Bloomington Drosophila Stock Center (NIH P40OD018537); the Vienna Drosophila Resource Center (VDRC, www.vdrc.at) and the Developmental Studies Hybridoma Bank for providing fly stocks and antibodies. We thank Alicia Alfonso Gomez for help with fly handling, experimental support and image acquisition. We also thank the Core Facilities for Advanced Light Microscopy and Advanced Electron Microscopy at Oslo University Hospital and the Microscopy Rennes Imaging facility of the UMS Biosit, a member of the national infrastructure France-BioImaging, supported by the French National Research Agency (ANR-10-INBS-04).; ANR-20-CE13-0015,ACTRICE,Contribution des Jonctions Tricellulaires dans la Mécanique Epithéliale(2020) |
| Source: |
ISSN: 1544-9173. |
| Publisher Information: |
CCSD; Public Library of Science |
| Publication Year: |
2025 |
| Subject Terms: |
[SDV.CAN]Life Sciences [q-bio]/Cancer |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1371/journal.pbio.3002663.s001; info:eu-repo/semantics/altIdentifier/pmid/40294135; PUBMED: 40294135 |
| DOI: |
10.1371/journal.pbio.3002663 |
| Availability: |
https://hal.science/hal-05063728; https://hal.science/hal-05063728v1/document; https://hal.science/hal-05063728v1/file/journal.pbio.3002663.pdf; https://doi.org/10.1371/journal.pbio.3002663 |
| Rights: |
http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.8033361A |
| Database: |
BASE |