p120-catenin-dependent collective brain infiltration by glioma cell networks

Gritsenko, P. G.; Atlasy, N.; Dieteren, C. E. J.; Navis, A. C.; Venhuizen, J. H.; Veelken, C.; Schubert, D.; Acker-Palmer, Amparo; Westerman, B. A.; Wurdinger, T.; Leenders, W.; Wesseling, P.; Stunnenberg, H. G.; Friedl, P.

doi:10.1038/s41556-019-0443-x

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p120-catenin-dependent collective brain infiltration by glioma cell networks

Gritsenko, P. G., Atlasy, N., Dieteren, C. E. J., Navis, A. C., Venhuizen, J. H., Veelken, C., et al. (2020). p120-catenin-dependent collective brain infiltration by glioma cell networks. Nat Cell Biol, 22(1), 97-107. doi:10.1038/s41556-019-0443-x.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0008-0C1C-D Version Permalink: https://hdl.handle.net/21.11116/0000-0008-0C1D-C

Genre: Journal Article

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https://www.ncbi.nlm.nih.gov/pubmed/31907411 (Any fulltext) Open Access status unknown

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Creators:
Gritsenko, P. G., Author
Atlasy, N., Author
Dieteren, C. E. J., Author
Navis, A. C., Author
Venhuizen, J. H., Author
Veelken, C., Author
Schubert, D., Author
Acker-Palmer, Amparo¹, Author
Westerman, B. A., Author
Wurdinger, T., Author
Leenders, W., Author
Wesseling, P., Author
Stunnenberg, H. G., Author
Friedl, P., Author

Affiliations:
1Neurovascular interface Group, Max Planck Institute for Brain Research, Max Planck Society, ou_2461707

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Free keywords: Adherens Junctions/*metabolism Animals Brain/metabolism/pathology Cadherins/metabolism Catenins/*metabolism Cell Adhesion/*physiology Cell Line, Tumor Down-Regulation/physiology Glioma/metabolism/*pathology Phosphoproteins/metabolism Phosphorylation

Abstract: Diffuse brain infiltration by glioma cells causes detrimental disease progression, but its multicellular coordination is poorly understood. We show here that glioma cells infiltrate the brain collectively as multicellular networks. Contacts between moving glioma cells are adaptive epithelial-like or filamentous junctions stabilized by N-cadherin, beta-catenin and p120-catenin, which undergo kinetic turnover, transmit intercellular calcium transients and mediate directional persistence. Downregulation of p120-catenin compromises cell-cell interaction and communication, disrupts collective networks, and both the cadherin and RhoA binding domains of p120-catenin are required for network formation and migration. Deregulating p120-catenin further prevents diffuse glioma cell infiltration of the mouse brain with marginalized microlesions as the outcome. Transcriptomics analysis has identified p120-catenin as an upstream regulator of neurogenesis and cell cycle pathways and a predictor of poor clinical outcome in glioma patients. Collective glioma networks infiltrating the brain thus depend on adherens junctions dynamics, the targeting of which may offer an unanticipated strategy to halt glioma progression.

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Dates: Date issued: 2020-01-08

Publication Status: Issued

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Identifiers: Other: 31907411
DOI: 10.1038/s41556-019-0443-x
ISSN: 1476-4679 (Electronic)1465-7392 (Linking)

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Title: Nat Cell Biol

Source Genre: Journal

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Pages: - Volume / Issue: 22 (1) Sequence Number: - Start / End Page: 97 - 107 Identifier: -