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N-WASP coordinates the delivery and F-actin–mediated capture of MT1-MMP at invasive pseudopods
Metastasizing tumor cells use matrix metalloproteases, such as the transmembrane collagenase MT1-MMP, together with actin-based protrusions, to break through extracellular matrix barriers and migrate in dense matrix. Here we show that the actin nucleation–promoting protein N-WASP (Neural Wiskott-Ald...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483131/ https://www.ncbi.nlm.nih.gov/pubmed/23091069 http://dx.doi.org/10.1083/jcb.201203025 |
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author | Yu, Xinzi Zech, Tobias McDonald, Laura Gonzalez, Esther Garcia Li, Ang Macpherson, Iain Schwarz, Juliane P. Spence, Heather Futó, Kinga Timpson, Paul Nixon, Colin Ma, Yafeng Anton, Ines M. Visegrády, Balázs Insall, Robert H. Oien, Karin Blyth, Karen Norman, Jim C. Machesky, Laura M. |
author_facet | Yu, Xinzi Zech, Tobias McDonald, Laura Gonzalez, Esther Garcia Li, Ang Macpherson, Iain Schwarz, Juliane P. Spence, Heather Futó, Kinga Timpson, Paul Nixon, Colin Ma, Yafeng Anton, Ines M. Visegrády, Balázs Insall, Robert H. Oien, Karin Blyth, Karen Norman, Jim C. Machesky, Laura M. |
author_sort | Yu, Xinzi |
collection | PubMed |
description | Metastasizing tumor cells use matrix metalloproteases, such as the transmembrane collagenase MT1-MMP, together with actin-based protrusions, to break through extracellular matrix barriers and migrate in dense matrix. Here we show that the actin nucleation–promoting protein N-WASP (Neural Wiskott-Aldrich syndrome protein) is up-regulated in breast cancer, and has a pivotal role in mediating the assembly of elongated pseudopodia that are instrumental in matrix degradation. Although a role for N-WASP in invadopodia was known, we now show how N-WASP regulates invasive protrusion in 3D matrices. In actively invading cells, N-WASP promoted trafficking of MT1-MMP into invasive pseudopodia, primarily from late endosomes, from which it was delivered to the plasma membrane. Upon MT1-MMP’s arrival at the plasma membrane in pseudopodia, N-WASP stabilized MT1-MMP via direct tethering of its cytoplasmic tail to F-actin. Thus, N-WASP is crucial for extension of invasive pseudopods into which MT1-MMP traffics and for providing the correct cytoskeletal framework to couple matrix remodeling with protrusive invasion. |
format | Online Article Text |
id | pubmed-3483131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-34831312013-04-29 N-WASP coordinates the delivery and F-actin–mediated capture of MT1-MMP at invasive pseudopods Yu, Xinzi Zech, Tobias McDonald, Laura Gonzalez, Esther Garcia Li, Ang Macpherson, Iain Schwarz, Juliane P. Spence, Heather Futó, Kinga Timpson, Paul Nixon, Colin Ma, Yafeng Anton, Ines M. Visegrády, Balázs Insall, Robert H. Oien, Karin Blyth, Karen Norman, Jim C. Machesky, Laura M. J Cell Biol Research Articles Metastasizing tumor cells use matrix metalloproteases, such as the transmembrane collagenase MT1-MMP, together with actin-based protrusions, to break through extracellular matrix barriers and migrate in dense matrix. Here we show that the actin nucleation–promoting protein N-WASP (Neural Wiskott-Aldrich syndrome protein) is up-regulated in breast cancer, and has a pivotal role in mediating the assembly of elongated pseudopodia that are instrumental in matrix degradation. Although a role for N-WASP in invadopodia was known, we now show how N-WASP regulates invasive protrusion in 3D matrices. In actively invading cells, N-WASP promoted trafficking of MT1-MMP into invasive pseudopodia, primarily from late endosomes, from which it was delivered to the plasma membrane. Upon MT1-MMP’s arrival at the plasma membrane in pseudopodia, N-WASP stabilized MT1-MMP via direct tethering of its cytoplasmic tail to F-actin. Thus, N-WASP is crucial for extension of invasive pseudopods into which MT1-MMP traffics and for providing the correct cytoskeletal framework to couple matrix remodeling with protrusive invasion. The Rockefeller University Press 2012-10-29 /pmc/articles/PMC3483131/ /pubmed/23091069 http://dx.doi.org/10.1083/jcb.201203025 Text en © 2012 Yu et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Yu, Xinzi Zech, Tobias McDonald, Laura Gonzalez, Esther Garcia Li, Ang Macpherson, Iain Schwarz, Juliane P. Spence, Heather Futó, Kinga Timpson, Paul Nixon, Colin Ma, Yafeng Anton, Ines M. Visegrády, Balázs Insall, Robert H. Oien, Karin Blyth, Karen Norman, Jim C. Machesky, Laura M. N-WASP coordinates the delivery and F-actin–mediated capture of MT1-MMP at invasive pseudopods |
title | N-WASP coordinates the delivery and F-actin–mediated capture of MT1-MMP at invasive pseudopods |
title_full | N-WASP coordinates the delivery and F-actin–mediated capture of MT1-MMP at invasive pseudopods |
title_fullStr | N-WASP coordinates the delivery and F-actin–mediated capture of MT1-MMP at invasive pseudopods |
title_full_unstemmed | N-WASP coordinates the delivery and F-actin–mediated capture of MT1-MMP at invasive pseudopods |
title_short | N-WASP coordinates the delivery and F-actin–mediated capture of MT1-MMP at invasive pseudopods |
title_sort | n-wasp coordinates the delivery and f-actin–mediated capture of mt1-mmp at invasive pseudopods |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483131/ https://www.ncbi.nlm.nih.gov/pubmed/23091069 http://dx.doi.org/10.1083/jcb.201203025 |
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