Endosomal WASH and exocyst complexes control exocytosis of MT1-MMP at invadopodia
Remodeling of the extracellular matrix by carcinoma cells during metastatic dissemination requires formation of actin-based protrusions of the plasma membrane called invadopodia, where the trans-membrane type 1 matrix metalloproteinase (MT1-MMP) accumulates. Here, we describe an interaction between...
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| Veröffentlicht in: | The Journal of cell biology 2013-12, Vol.203 (6), p.1063-1079 |
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| creator | Monteiro, Pedro Rossé, Carine Castro-Castro, Antonio Irondelle, Marie Lagoutte, Emilie Paul-Gilloteaux, Perrine Desnos, Claire Formstecher, Etienne Darchen, François Perrais, David Gautreau, Alexis Hertzog, Maud Chavrier, Philippe |
| description | Remodeling of the extracellular matrix by carcinoma cells during metastatic dissemination requires formation of actin-based protrusions of the plasma membrane called invadopodia, where the trans-membrane type 1 matrix metalloproteinase (MT1-MMP) accumulates. Here, we describe an interaction between the exocyst complex and the endosomal Arp2/3 activator Wiskott-Aldrich syndrome protein and Scar homolog (WASH) on MT1-MMP–containing late endosomes in invasive breast carcinoma cells. We found that WASH and exocyst are required for matrix degradation by an exocytic mechanism that involves tubular connections between MT1-MMP–positive late endosomes and the plasma membrane in contact with the matrix. This ensures focal delivery of MT1-MMP and supports pericellular matrix degradation and tumor cell invasion into different pathologically relevant matrix environments. Our data suggest a general mechanism used by tumor cells to breach the basement membrane and for invasive migration through fibrous collagen-enriched tissues surrounding the tumor. |
| doi_str_mv | 10.1083/jcb.201306162 |
| format | Article |
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Here, we describe an interaction between the exocyst complex and the endosomal Arp2/3 activator Wiskott-Aldrich syndrome protein and Scar homolog (WASH) on MT1-MMP–containing late endosomes in invasive breast carcinoma cells. We found that WASH and exocyst are required for matrix degradation by an exocytic mechanism that involves tubular connections between MT1-MMP–positive late endosomes and the plasma membrane in contact with the matrix. This ensures focal delivery of MT1-MMP and supports pericellular matrix degradation and tumor cell invasion into different pathologically relevant matrix environments. Our data suggest a general mechanism used by tumor cells to breach the basement membrane and for invasive migration through fibrous collagen-enriched tissues surrounding the tumor.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.201306162</identifier><identifier>PMID: 24344185</identifier><identifier>CODEN: JCLBA3</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Adenocarcinoma - pathology ; Breast cancer ; Breast Neoplasms - pathology ; Cells ; Collagen ; Endosomes - metabolism ; Exocytosis ; Extracellular Matrix - metabolism ; Extracellular Matrix - ultrastructure ; Female ; Humans ; Life Sciences ; Matrix Metalloproteinase 14 - metabolism ; Membranes ; Microfilament Proteins - metabolism ; Microfilament Proteins - physiology ; Models, Biological ; Neoplasm Invasiveness ; Neoplasm Metastasis - pathology ; Neoplasm Metastasis - ultrastructure ; Proteins ; Tissues ; Tumors ; Vesicular Transport Proteins - metabolism ; Vesicular Transport Proteins - physiology</subject><ispartof>The Journal of cell biology, 2013-12, Vol.203 (6), p.1063-1079</ispartof><rights>Copyright Rockefeller University Press Dec 23, 2013</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2013 Monteiro et al. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c515t-18888ae0773df816be853a9d77630a8177db2a4699dcb66b70a9875fdaad119a3</citedby><cites>FETCH-LOGICAL-c515t-18888ae0773df816be853a9d77630a8177db2a4699dcb66b70a9875fdaad119a3</cites><orcidid>0000-0002-2369-4362 ; 0000-0001-6732-7233 ; 0000-0002-5878-5408 ; 0000-0002-4822-165X ; 0000-0002-7351-733X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24344185$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01712237$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Monteiro, Pedro</creatorcontrib><creatorcontrib>Rossé, Carine</creatorcontrib><creatorcontrib>Castro-Castro, Antonio</creatorcontrib><creatorcontrib>Irondelle, Marie</creatorcontrib><creatorcontrib>Lagoutte, Emilie</creatorcontrib><creatorcontrib>Paul-Gilloteaux, Perrine</creatorcontrib><creatorcontrib>Desnos, Claire</creatorcontrib><creatorcontrib>Formstecher, Etienne</creatorcontrib><creatorcontrib>Darchen, François</creatorcontrib><creatorcontrib>Perrais, David</creatorcontrib><creatorcontrib>Gautreau, Alexis</creatorcontrib><creatorcontrib>Hertzog, Maud</creatorcontrib><creatorcontrib>Chavrier, Philippe</creatorcontrib><title>Endosomal WASH and exocyst complexes control exocytosis of MT1-MMP at invadopodia</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>Remodeling of the extracellular matrix by carcinoma cells during metastatic dissemination requires formation of actin-based protrusions of the plasma membrane called invadopodia, where the trans-membrane type 1 matrix metalloproteinase (MT1-MMP) accumulates. 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| subjects | Adenocarcinoma - pathology Breast cancer Breast Neoplasms - pathology Cells Collagen Endosomes - metabolism Exocytosis Extracellular Matrix - metabolism Extracellular Matrix - ultrastructure Female Humans Life Sciences Matrix Metalloproteinase 14 - metabolism Membranes Microfilament Proteins - metabolism Microfilament Proteins - physiology Models, Biological Neoplasm Invasiveness Neoplasm Metastasis - pathology Neoplasm Metastasis - ultrastructure Proteins Tissues Tumors Vesicular Transport Proteins - metabolism Vesicular Transport Proteins - physiology |
| title | Endosomal WASH and exocyst complexes control exocytosis of MT1-MMP at invadopodia |
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