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Direct inhibition of myosin II effectively blocks glioma invasion in the presence of multiple motogens
Anaplastic gliomas, the most common and malignant of primary brain tumors, frequently contain activating mutations and amplifications in promigratory signal transduction pathways. However, targeting these pathways with individual signal transduction inhibitors does not appreciably reduce tumor invas...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279383/ https://www.ncbi.nlm.nih.gov/pubmed/22219380 http://dx.doi.org/10.1091/mbc.E11-01-0039 |
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author | Ivkovic, Sanja Beadle, Christopher Noticewala, Sonal Massey, Susan C. Swanson, Kristin R. Toro, Laura N. Bresnick, Anne R. Canoll, Peter Rosenfeld, Steven S. |
author_facet | Ivkovic, Sanja Beadle, Christopher Noticewala, Sonal Massey, Susan C. Swanson, Kristin R. Toro, Laura N. Bresnick, Anne R. Canoll, Peter Rosenfeld, Steven S. |
author_sort | Ivkovic, Sanja |
collection | PubMed |
description | Anaplastic gliomas, the most common and malignant of primary brain tumors, frequently contain activating mutations and amplifications in promigratory signal transduction pathways. However, targeting these pathways with individual signal transduction inhibitors does not appreciably reduce tumor invasion, because these pathways are redundant; blockade of any one pathway can be overcome by stimulation of another. This implies that a more effective approach would be to target a component at which these pathways converge. In this study, we have investigated whether the molecular motor myosin II represents such a target by examining glioma invasion in a series of increasingly complex models that are sensitive to platelet-derived growth factor, epidermal growth factor, or both. Our results lead to two conclusions. First, malignant glioma cells are stimulated to invade brain through the activation of multiple signaling cascades not accounted for in simple in vitro assays. Second, even though there is a high degree of redundancy in promigratory signaling cascades in gliomas, blocking tumor invasion by directly targeting myosin II remains effective. Our results thus support our hypothesis that myosin II represents a point of convergence for signal transduction pathways that drive glioma invasion and that its inhibition cannot be overcome by other motility mechanisms. |
format | Online Article Text |
id | pubmed-3279383 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-32793832012-04-30 Direct inhibition of myosin II effectively blocks glioma invasion in the presence of multiple motogens Ivkovic, Sanja Beadle, Christopher Noticewala, Sonal Massey, Susan C. Swanson, Kristin R. Toro, Laura N. Bresnick, Anne R. Canoll, Peter Rosenfeld, Steven S. Mol Biol Cell Articles Anaplastic gliomas, the most common and malignant of primary brain tumors, frequently contain activating mutations and amplifications in promigratory signal transduction pathways. However, targeting these pathways with individual signal transduction inhibitors does not appreciably reduce tumor invasion, because these pathways are redundant; blockade of any one pathway can be overcome by stimulation of another. This implies that a more effective approach would be to target a component at which these pathways converge. In this study, we have investigated whether the molecular motor myosin II represents such a target by examining glioma invasion in a series of increasingly complex models that are sensitive to platelet-derived growth factor, epidermal growth factor, or both. Our results lead to two conclusions. First, malignant glioma cells are stimulated to invade brain through the activation of multiple signaling cascades not accounted for in simple in vitro assays. Second, even though there is a high degree of redundancy in promigratory signaling cascades in gliomas, blocking tumor invasion by directly targeting myosin II remains effective. Our results thus support our hypothesis that myosin II represents a point of convergence for signal transduction pathways that drive glioma invasion and that its inhibition cannot be overcome by other motility mechanisms. The American Society for Cell Biology 2012-02-15 /pmc/articles/PMC3279383/ /pubmed/22219380 http://dx.doi.org/10.1091/mbc.E11-01-0039 Text en © 2012 Ivkovic et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Ivkovic, Sanja Beadle, Christopher Noticewala, Sonal Massey, Susan C. Swanson, Kristin R. Toro, Laura N. Bresnick, Anne R. Canoll, Peter Rosenfeld, Steven S. Direct inhibition of myosin II effectively blocks glioma invasion in the presence of multiple motogens |
title | Direct inhibition of myosin II effectively blocks glioma invasion in the presence of multiple motogens |
title_full | Direct inhibition of myosin II effectively blocks glioma invasion in the presence of multiple motogens |
title_fullStr | Direct inhibition of myosin II effectively blocks glioma invasion in the presence of multiple motogens |
title_full_unstemmed | Direct inhibition of myosin II effectively blocks glioma invasion in the presence of multiple motogens |
title_short | Direct inhibition of myosin II effectively blocks glioma invasion in the presence of multiple motogens |
title_sort | direct inhibition of myosin ii effectively blocks glioma invasion in the presence of multiple motogens |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279383/ https://www.ncbi.nlm.nih.gov/pubmed/22219380 http://dx.doi.org/10.1091/mbc.E11-01-0039 |
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