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Plexin-B2 facilitates glioblastoma infiltration by modulating cell biomechanics
Infiltrative growth is a major cause of high lethality of malignant brain tumors such as glioblastoma (GBM). We show here that GBM cells upregulate guidance receptor Plexin-B2 to gain invasiveness. Deletion of Plexin-B2 in GBM stem cells limited tumor spread and shifted invasion paths from axon fibe...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846610/ https://www.ncbi.nlm.nih.gov/pubmed/33514835 http://dx.doi.org/10.1038/s42003-021-01667-4 |
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author | Huang, Yong Tejero, Rut Lee, Vivian K. Brusco, Concetta Hannah, Theodore Bertucci, Taylor B. Junqueira Alves, Chrystian Katsyv, Igor Kluge, Michael Foty, Ramsey Zhang, Bin Friedel, Caroline C. Dai, Guohao Zou, Hongyan Friedel, Roland H. |
author_facet | Huang, Yong Tejero, Rut Lee, Vivian K. Brusco, Concetta Hannah, Theodore Bertucci, Taylor B. Junqueira Alves, Chrystian Katsyv, Igor Kluge, Michael Foty, Ramsey Zhang, Bin Friedel, Caroline C. Dai, Guohao Zou, Hongyan Friedel, Roland H. |
author_sort | Huang, Yong |
collection | PubMed |
description | Infiltrative growth is a major cause of high lethality of malignant brain tumors such as glioblastoma (GBM). We show here that GBM cells upregulate guidance receptor Plexin-B2 to gain invasiveness. Deletion of Plexin-B2 in GBM stem cells limited tumor spread and shifted invasion paths from axon fiber tracts to perivascular routes. On a cellular level, Plexin-B2 adjusts cell adhesiveness, migratory responses to different matrix stiffness, and actomyosin dynamics, thus empowering GBM cells to leave stiff tumor bulk and infiltrate softer brain parenchyma. Correspondingly, gene signatures affected by Plexin-B2 were associated with locomotor regulation, matrix interactions, and cellular biomechanics. On a molecular level, the intracellular Ras-GAP domain contributed to Plexin-B2 function, while the signaling relationship with downstream effectors Rap1/2 appeared variable between GBM stem cell lines, reflecting intertumoral heterogeneity. Our studies establish Plexin-B2 as a modulator of cell biomechanics that is usurped by GBM cells to gain invasiveness. |
format | Online Article Text |
id | pubmed-7846610 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78466102021-02-08 Plexin-B2 facilitates glioblastoma infiltration by modulating cell biomechanics Huang, Yong Tejero, Rut Lee, Vivian K. Brusco, Concetta Hannah, Theodore Bertucci, Taylor B. Junqueira Alves, Chrystian Katsyv, Igor Kluge, Michael Foty, Ramsey Zhang, Bin Friedel, Caroline C. Dai, Guohao Zou, Hongyan Friedel, Roland H. Commun Biol Article Infiltrative growth is a major cause of high lethality of malignant brain tumors such as glioblastoma (GBM). We show here that GBM cells upregulate guidance receptor Plexin-B2 to gain invasiveness. Deletion of Plexin-B2 in GBM stem cells limited tumor spread and shifted invasion paths from axon fiber tracts to perivascular routes. On a cellular level, Plexin-B2 adjusts cell adhesiveness, migratory responses to different matrix stiffness, and actomyosin dynamics, thus empowering GBM cells to leave stiff tumor bulk and infiltrate softer brain parenchyma. Correspondingly, gene signatures affected by Plexin-B2 were associated with locomotor regulation, matrix interactions, and cellular biomechanics. On a molecular level, the intracellular Ras-GAP domain contributed to Plexin-B2 function, while the signaling relationship with downstream effectors Rap1/2 appeared variable between GBM stem cell lines, reflecting intertumoral heterogeneity. Our studies establish Plexin-B2 as a modulator of cell biomechanics that is usurped by GBM cells to gain invasiveness. Nature Publishing Group UK 2021-01-29 /pmc/articles/PMC7846610/ /pubmed/33514835 http://dx.doi.org/10.1038/s42003-021-01667-4 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Huang, Yong Tejero, Rut Lee, Vivian K. Brusco, Concetta Hannah, Theodore Bertucci, Taylor B. Junqueira Alves, Chrystian Katsyv, Igor Kluge, Michael Foty, Ramsey Zhang, Bin Friedel, Caroline C. Dai, Guohao Zou, Hongyan Friedel, Roland H. Plexin-B2 facilitates glioblastoma infiltration by modulating cell biomechanics |
title | Plexin-B2 facilitates glioblastoma infiltration by modulating cell biomechanics |
title_full | Plexin-B2 facilitates glioblastoma infiltration by modulating cell biomechanics |
title_fullStr | Plexin-B2 facilitates glioblastoma infiltration by modulating cell biomechanics |
title_full_unstemmed | Plexin-B2 facilitates glioblastoma infiltration by modulating cell biomechanics |
title_short | Plexin-B2 facilitates glioblastoma infiltration by modulating cell biomechanics |
title_sort | plexin-b2 facilitates glioblastoma infiltration by modulating cell biomechanics |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846610/ https://www.ncbi.nlm.nih.gov/pubmed/33514835 http://dx.doi.org/10.1038/s42003-021-01667-4 |
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