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Cell–cell adhesion and 3D matrix confinement determine jamming transitions in breast cancer invasion
Open accessAbstract
Plasticity of cancer invasion and metastasis depends on the ability of cancer cells to switch between collective and single-cell dissemination, controlled by cadherin-mediated cell-cell junctions. In clinical samples, E-cadherin-expressing and -deficient tumours both invade collectively and metastasize equally, implicating additional mechanisms controlling cell-cell cooperation and individualization. Here, using spatially defined organotypic culture, intravital microscopy of mammary tumours in mice and in silico modelling, we identify cell density regulation by three-dimensional tissue boundaries to physically control collective movement irrespective of the composition and stability of cell-cell junctions. Deregulation of adherens junctions by downregulation of E-cadherin and p120-catenin resulted in a transition from coordinated to uncoordinated collective movement along extracellular boundaries, whereas single-cell escape depended on locally free tissue space. These results indicate that cadherins and extracellular matrix confinement cooperate to determine unjamming transitions and stepwise epithelial fluidization towards, ultimately, cell individualization.
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“More recently, however, efforts have been made to design anisotropic matrix structures (including in CoC devices) in particular, but not exclusively, collagen type I [24], with the aim of recapitulating in vivo-like aligned collagen-rich ECM interacting with invasive tumors [25] by using (i) engineered, (ii) directional force-derived, or (iii) cell-derived approaches (Figure 2A-C and Table 1).”
From Cancer-on-chip models for metastasis: importance of the tumor microenvironment (2024) · cites this paper as [25]
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Metadata
- Authors
- Ilina, O., Gritsenko, P. G., Syga, S., Lippoldt, J., La Porta, C. A. M., Chepizhko, O., Grosser, S., Vullings, M., Bakker, G.-J., Starruß, J., Bult, P., Zapperi, S., Käs, J. A., Deutsch, A., & Friedl, P.
- Affiliations
- Radboud University Medical Center (NL)
- Center for Information Services and High Performance Computing (DE)
- Leipzig University (DE)
- Universität Innsbruck (AT)
- University of Milan (IT)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Friedl, Peter
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2020-08-24
- Volume
- 22
- Issue
- 9
- Pages
- 1103-1115
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC7502685
- OpenAlex
- W3080611254
- Cited by
- 375
- References
- 67
- Citations by year
- 2026: 45 · 2025: 69 · 2024: 60 · 2023: 61 · 2022: 53 · 2021: 74 · 2020: 10
- FWCI
- 24.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (918.11.626)
- National Cancer Institute (U54CA210184, P30CA016672)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- cell-cell adhesion, E-cadherin, p120 catenin, adherens junctions, collective cell migration, breast cancer invasion, metastasis, tissue boundaries, cell density regulation, unjamming transition, organotypic culture, intravital microscopy, in silico modeling
- MeSH terms
- Animals, Breast Neoplasms, Cell Adhesion, Cell Line, Female, Humans, Intercellular Junctions, Mice, Inbred BALB C, Neoplasm Invasiveness, Down-Regulation, Gene Expression Regulation, Neoplastic, Adherens Junctions, Cell Line, Tumor, HEK293 Cells, MCF-7 Cells
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