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Cell–cell adhesion and 3D matrix confinement determine jamming transitions in breast cancer invasion
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 metastas...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502685/ https://www.ncbi.nlm.nih.gov/pubmed/32839548 http://dx.doi.org/10.1038/s41556-020-0552-6 |
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author | Ilina, Olga Gritsenko, Pavlo G. Syga, Simon Lippoldt, Jürgen La Porta, Caterina A. M. Chepizhko, Oleksandr Grosser, Steffen Vullings, Manon Bakker, Gert-Jan Starruß, Jörn Bult, Peter Zapperi, Stefano Käs, Josef A. Deutsch, Andreas Friedl, Peter |
author_facet | Ilina, Olga Gritsenko, Pavlo G. Syga, Simon Lippoldt, Jürgen La Porta, Caterina A. M. Chepizhko, Oleksandr Grosser, Steffen Vullings, Manon Bakker, Gert-Jan Starruß, Jörn Bult, Peter Zapperi, Stefano Käs, Josef A. Deutsch, Andreas Friedl, Peter |
author_sort | Ilina, Olga |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7502685 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-75026852021-02-24 Cell–cell adhesion and 3D matrix confinement determine jamming transitions in breast cancer invasion Ilina, Olga Gritsenko, Pavlo G. Syga, Simon Lippoldt, Jürgen La Porta, Caterina A. M. Chepizhko, Oleksandr Grosser, Steffen Vullings, Manon Bakker, Gert-Jan Starruß, Jörn Bult, Peter Zapperi, Stefano Käs, Josef A. Deutsch, Andreas Friedl, Peter Nat Cell Biol Article 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. 2020-08-24 2020-09 /pmc/articles/PMC7502685/ /pubmed/32839548 http://dx.doi.org/10.1038/s41556-020-0552-6 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Ilina, Olga Gritsenko, Pavlo G. Syga, Simon Lippoldt, Jürgen La Porta, Caterina A. M. Chepizhko, Oleksandr Grosser, Steffen Vullings, Manon Bakker, Gert-Jan Starruß, Jörn Bult, Peter Zapperi, Stefano Käs, Josef A. Deutsch, Andreas Friedl, Peter Cell–cell adhesion and 3D matrix confinement determine jamming transitions in breast cancer invasion |
title | Cell–cell adhesion and 3D matrix confinement determine jamming transitions in breast cancer invasion |
title_full | Cell–cell adhesion and 3D matrix confinement determine jamming transitions in breast cancer invasion |
title_fullStr | Cell–cell adhesion and 3D matrix confinement determine jamming transitions in breast cancer invasion |
title_full_unstemmed | Cell–cell adhesion and 3D matrix confinement determine jamming transitions in breast cancer invasion |
title_short | Cell–cell adhesion and 3D matrix confinement determine jamming transitions in breast cancer invasion |
title_sort | cell–cell adhesion and 3d matrix confinement determine jamming transitions in breast cancer invasion |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502685/ https://www.ncbi.nlm.nih.gov/pubmed/32839548 http://dx.doi.org/10.1038/s41556-020-0552-6 |
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