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

Autor: Gritsenko PG; Department of Cell Biology, Radboud University Medical Center, Nijmegen, The Netherlands., Atlasy N; Department of Molecular Biology, Radboud University, Nijmegen, The Netherlands.; Center for Molecular Medicine, University Medical Center, Utrecht, The Netherlands., Dieteren CEJ; Department of Cell Biology, Radboud University Medical Center, Nijmegen, The Netherlands.; Protinhi Therapeutics, Nijmegen, The Netherlands., Navis AC; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden., Venhuizen JH; Department of Cell Biology, Radboud University Medical Center, Nijmegen, The Netherlands., Veelken C; Department of Cell Biology, Radboud University Medical Center, Nijmegen, The Netherlands., Schubert D; Cognitive Neuroscience Department, Donders Institute, Radboud University Medical Center, Nijmegen, The Netherlands., Acker-Palmer A; Institute of Cell Biology and Neuroscience and BMLS, Goethe University Frankfurt, Frankfurt, Germany.; Max Planck Institute for Brain Research, Frankfurt, Germany., Westerman BA; Department of Neurosurgery, VU University Medical Center, Amsterdam, The Netherlands., Wurdinger T; Department of Neurosurgery, VU University Medical Center, Amsterdam, The Netherlands., Leenders W; Department of Biochemistry, Radboud University Medical Center, Nijmegen, The Netherlands., Wesseling P; Department of Pathology, Amsterdam University Medical Centers/VUmc and Brain Tumor Center Amsterdam, Amsterdam, The Netherlands.; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Stunnenberg HG; Department of Molecular Biology, Radboud University, Nijmegen, The Netherlands.; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Friedl P; Department of Cell Biology, Radboud University Medical Center, Nijmegen, The Netherlands. Peter.Friedl@radboudumc.nl.; The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Peter.Friedl@radboudumc.nl.; Cancer Genomics Center, Utrecht, The Netherlands. Peter.Friedl@radboudumc.nl.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2020 Jan; Vol. 22 (1), pp. 97-107. Date of Electronic Publication: 2020 Jan 06.
DOI: 10.1038/s41556-019-0443-x
Abstrakt: 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: MEDLINE
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