Open AccessCell–cell adhesion and 3D matrix confinement determine jamming transitions in breast cancer invasion
Author(s) -
Olga Ilina,
Pavlo G. Gritsenko,
Simon Syga,
Jürgen Lippoldt,
Caterina A. M. La Porta,
Oleksandr Chepizhko,
Steffen Grosser,
Ma Vullings,
Gert-Jan Bakker,
Jörn Starruß,
Peter Bult,
Stefano Zapperi,
Josef A. Käs,
Andreas Deutsch,
Peter Friedl
Publication year - 2020
Publication title -
nature cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 11.38
H-Index - 369
eISSN - 1476-4679
pISSN - 1465-7392
DOI - 10.1038/s41556-020-0552-6
Subject(s) - adherens junction , microbiology and biotechnology , cadherin , extracellular matrix , cancer cell , cell , cell adhesion , biology , cell junction , cell migration , cancer , genetics
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.