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Dense fibrillar collagen is a potent inducer of invadopodia via a specific signaling network
Cell interactions with the extracellular matrix (ECM) can regulate multiple cellular activities and the matrix itself in dynamic, bidirectional processes. One such process is local proteolytic modification of the ECM. Invadopodia of tumor cells are actin-rich proteolytic protrusions that locally deg...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315243/ https://www.ncbi.nlm.nih.gov/pubmed/25646088 http://dx.doi.org/10.1083/jcb.201405099 |
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author | Artym, Vira V. Swatkoski, Stephen Matsumoto, Kazue Campbell, Catherine B. Petrie, Ryan J. Dimitriadis, Emilios K. Li, Xin Mueller, Susette C. Bugge, Thomas H. Gucek, Marjan Yamada, Kenneth M. |
author_facet | Artym, Vira V. Swatkoski, Stephen Matsumoto, Kazue Campbell, Catherine B. Petrie, Ryan J. Dimitriadis, Emilios K. Li, Xin Mueller, Susette C. Bugge, Thomas H. Gucek, Marjan Yamada, Kenneth M. |
author_sort | Artym, Vira V. |
collection | PubMed |
description | Cell interactions with the extracellular matrix (ECM) can regulate multiple cellular activities and the matrix itself in dynamic, bidirectional processes. One such process is local proteolytic modification of the ECM. Invadopodia of tumor cells are actin-rich proteolytic protrusions that locally degrade matrix molecules and mediate invasion. We report that a novel high-density fibrillar collagen (HDFC) matrix is a potent inducer of invadopodia, both in carcinoma cell lines and in primary human fibroblasts. In carcinoma cells, HDFC matrix induced formation of invadopodia via a specific integrin signaling pathway that did not require growth factors or even altered gene and protein expression. In contrast, phosphoproteomics identified major changes in a complex phosphosignaling network with kindlin2 serine phosphorylation as a key regulatory element. This kindlin2-dependent signal transduction network was required for efficient induction of invadopodia on dense fibrillar collagen and for local degradation of collagen. This novel phosphosignaling mechanism regulates cell surface invadopodia via kindlin2 for local proteolytic remodeling of the ECM. |
format | Online Article Text |
id | pubmed-4315243 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-43152432015-08-02 Dense fibrillar collagen is a potent inducer of invadopodia via a specific signaling network Artym, Vira V. Swatkoski, Stephen Matsumoto, Kazue Campbell, Catherine B. Petrie, Ryan J. Dimitriadis, Emilios K. Li, Xin Mueller, Susette C. Bugge, Thomas H. Gucek, Marjan Yamada, Kenneth M. J Cell Biol Research Articles Cell interactions with the extracellular matrix (ECM) can regulate multiple cellular activities and the matrix itself in dynamic, bidirectional processes. One such process is local proteolytic modification of the ECM. Invadopodia of tumor cells are actin-rich proteolytic protrusions that locally degrade matrix molecules and mediate invasion. We report that a novel high-density fibrillar collagen (HDFC) matrix is a potent inducer of invadopodia, both in carcinoma cell lines and in primary human fibroblasts. In carcinoma cells, HDFC matrix induced formation of invadopodia via a specific integrin signaling pathway that did not require growth factors or even altered gene and protein expression. In contrast, phosphoproteomics identified major changes in a complex phosphosignaling network with kindlin2 serine phosphorylation as a key regulatory element. This kindlin2-dependent signal transduction network was required for efficient induction of invadopodia on dense fibrillar collagen and for local degradation of collagen. This novel phosphosignaling mechanism regulates cell surface invadopodia via kindlin2 for local proteolytic remodeling of the ECM. The Rockefeller University Press 2015-02-02 /pmc/articles/PMC4315243/ /pubmed/25646088 http://dx.doi.org/10.1083/jcb.201405099 Text en 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 Artym, Vira V. Swatkoski, Stephen Matsumoto, Kazue Campbell, Catherine B. Petrie, Ryan J. Dimitriadis, Emilios K. Li, Xin Mueller, Susette C. Bugge, Thomas H. Gucek, Marjan Yamada, Kenneth M. Dense fibrillar collagen is a potent inducer of invadopodia via a specific signaling network |
title | Dense fibrillar collagen is a potent inducer of invadopodia via a specific signaling network |
title_full | Dense fibrillar collagen is a potent inducer of invadopodia via a specific signaling network |
title_fullStr | Dense fibrillar collagen is a potent inducer of invadopodia via a specific signaling network |
title_full_unstemmed | Dense fibrillar collagen is a potent inducer of invadopodia via a specific signaling network |
title_short | Dense fibrillar collagen is a potent inducer of invadopodia via a specific signaling network |
title_sort | dense fibrillar collagen is a potent inducer of invadopodia via a specific signaling network |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315243/ https://www.ncbi.nlm.nih.gov/pubmed/25646088 http://dx.doi.org/10.1083/jcb.201405099 |
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