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

Autor: Bart A. Westerman, Anna C. Navis, Jan Hendrik Venhuizen, Peter Friedl, Cindy E.J. Dieteren, Cornelia Veelken, Amparo Acker-Palmer, William P.J. Leenders, Dirk Schubert, Pavlo G. Gritsenko, Nader Atlasy, Pieter Wesseling, Hendrik G. Stunnenberg, Thomas Wurdinger
Přispěvatelé: Neurosurgery, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, Pathology, Academic Medical Center
Rok vydání: 2020
Předmět:
Delta Catenin
RHOA
Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2]
Cell
Down-Regulation
Biology
Article
Adherens junction
03 medical and health sciences
Diffuse Glioma
0302 clinical medicine
Cell Line
Tumor
Glioma
Cell Adhesion
medicine
Animals
Phosphorylation
Molecular Biology
030304 developmental biology
0303 health sciences
Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17]
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]
Cadherin
Neurogenesis
Brain
Catenins
Adherens Junctions
Cell Biology
Cell cycle
Cadherins
Phosphoproteins
medicine.disease
Cell biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
biology.protein
Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19]
Zdroj: Nature Cell Biology, 22, 1, pp. 97-107
Gritsenko, P G, Atlasy, N, Dieteren, C E J, Navis, A C, Venhuizen, J-H, Veelken, C, Schubert, D, Acker-Palmer, A, Westerman, B A, Wurdinger, T, Leenders, W, Wesseling, P, Stunnenberg, H G & Friedl, P 2020, ' p120-catenin-dependent collective brain infiltration by glioma cell networks ', Nature Cell Biology, vol. 22, no. 1, pp. 97-107 . https://doi.org/10.1038/s41556-019-0443-x
Nature Cell Biology, 22(1), 97-107. Nature Publishing Group
Nature Cell Biology, 22, 97-107
Nature cell biology, 22(1), 97-107. Nature Publishing Group
Nature cell biology
Nat Cell Biol
ISSN: 1465-7392
DOI: 10.1038/s41556-019-0443-x
Popis: Contains fulltext : 220594.pdf (Publisher’s version ) (Closed access) 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, β-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.
Databáze: OpenAIRE
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