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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...

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Autores principales: Ivkovic, Sanja, Beadle, Christopher, Noticewala, Sonal, Massey, Susan C., Swanson, Kristin R., Toro, Laura N., Bresnick, Anne R., Canoll, Peter, Rosenfeld, Steven S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
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.
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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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