期刊
JOURNAL OF CELL BIOLOGY
卷 203, 期 6, 页码 1063-1079出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201306162
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- Ligue Nationale contre le Cancer
- Fondation ARC pour la recherche sur le cancer
- Fondation ARC pour la recherche sur le cancer [SL220100601356]
- Agence Nationale pour la Recherche [ANR-08-BLAN-0111]
- GenHomme Network [02490-6088]
- Institut Curie
- Centre National de la Recherche Scientifique
- Agence Nationale de la Recherche (ANR) [ANR-08-BLAN-0111] Funding Source: Agence Nationale de la Recherche (ANR)
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 WiskottAldrich 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 MT1MMP- 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.
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