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Publication : Endosomal WASH and exocyst complexes control exocytosis of MT1-MMP at invadopodia.

First Author  Monteiro P Year  2013
Journal  J Cell Biol Volume  203
Issue  6 Pages  1063-79
PubMed ID  24344185 Mgi Jnum  J:208279
Mgi Id  MGI:5562599 Doi  10.1083/jcb.201306162
Citation  Monteiro P, et al. (2013) Endosomal WASH and exocyst complexes control exocytosis of MT1-MMP at invadopodia. J Cell Biol 203(6):1063-79
abstractText  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.
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