| Title: |
The directionality of collective cell delamination is governed by tissue architecture and cell adhesion in a Drosophila carcinoma model |
| Authors: |
Mira-Osuna, Marta; Plunder, Steffen; Theveneau, Eric; Le Borgne, Roland |
| Contributors: |
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); Kyōto daigaku = Kyoto University; Unité de biologie Moléculaire, Cellulaire et du Développement (MCD); Centre de Biologie Intégrative (CBI); Centre National de la Recherche Scientifique (CNRS)-Université de Toulouse (EPE UT); Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Centre National de la Recherche Scientifique (CNRS)-Université de Toulouse (EPE UT); Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Communauté d'universités et établissements de Toulouse (Comue de Toulouse); This work was supported by grants awarded to MMO by Ligue Nationale Contre le Cancer (IP/SC-16639) and Association pour la Recherche contre le Cancer (ARCDOC42023020006318). SP is supported by the KAKENHI Grant-in-Aid for Early-Career Scientists (Grant number 24K16962). E.T. is supported by ANR-21-CE13-0028-02 and the ARC (ARCPJA22020060002084). RLB is supported by the French National Research Agency (ANR-20-CE13-0015) and ARC (PJA 20191209388). BIOSIT is a member of the national infrastructure France-BioImaging, supported by the ANR (ANR-10-INBS-0004). We thank V. Auld, A. Bardin, S. Luschnig, T. Xu, and the Bloomington Stock Center and the National Institute of Genetics Fly Stock Center for providing fly lines. The monoclonal antibodies against Cora, E-cad, and β-Integrin were obtained from the Developmental Studies Hybridoma Bank, generated under the auspices of the National Institute of Child Health and Human Development, and maintained by the University of Iowa Department of Biological Sciences. We also thank S. Dutertre and X. Pinson from the Microscopy Rennes Imaging Center- BIOSIT. We are grateful to Chantal Roubinet and Caroline Dillard for their critical reading of the article.; ANR-20-CE13-0015,ACTRICE,Contribution des Jonctions Tricellulaires dans la Mécanique Epithéliale(2020); ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010); ANR-21-CE13-0028,SingleCrest,SINGLE CREST: Mosaïque cellulaire et crête neurale: impact sur la transition épithélium-mésenchyme.(2021) |
| Source: |
EISSN: 2589-0042 ; iScience ; https://hal.science/hal-05398825 ; iScience, 2025, 28 (11), pp.113663. ⟨10.1016/j.isci.2025.113663⟩ |
| Publisher Information: |
CCSD; Elsevier |
| Publication Year: |
2025 |
| Collection: |
Université Toulouse III - Paul Sabatier: HAL-UPS |
| Subject Terms: |
Cell biology; Cancer; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; Epithelial cells contact each other and the extracellular matrix via cell junctions, establishing mechanochemical barriers. During collective delamination, epithelia-derived tumors detach from the tissue with a directionality that dictates their malignancy. How cell junctions contribute to this process and how the directionality of delamination is regulated remains unknown. We used the Drosophila Ras V12 carcinoma model and found that the loss of septate junctions in epithelial cells triggers apoptosis, whereas in Ras V12 -cells promotes collective delamination. We found that apical and basal delamination differ in cell identity, polarity, and junctional remodeling, occurring exclusively in squamous and pseudostratified epithelia, respectively. We performed mathematical simulations using a 2D agent-based model and found that tissue architecture and preferential adhesion between mutant cells and with wild-type neighbors regulate the directionality of delamination. Apical delamination initiates with cells constricting apically, emitting apical protrusions, and forming an apical neck via preferential adhesion to collectively detach from the tissue. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://hal.science/hal-04779250; info:eu-repo/semantics/altIdentifier/pmid/41158866; BIORXIV: 2024.10.08.617152; PUBMED: 41158866; PUBMEDCENTRAL: PMC12555851 |
| DOI: |
10.1016/j.isci.2025.113663 |
| Availability: |
https://hal.science/hal-05398825; https://hal.science/hal-05398825v1/document; https://hal.science/hal-05398825v1/file/1-s2.0-S2589004225019248-main.pdf; https://doi.org/10.1016/j.isci.2025.113663 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.D3608EA6 |
| Database: |
BASE |