Endosomal WASH and exocyst complexes control exocytosis of MT1-MMP at invadopodia.
J Cell Biol. 2013-12-16; 203(6): 1063-1079
DOI: 10.1083/jcb.201306162
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1. J Cell Biol. 2013 Dec 23;203(6):1063-79.
Endosomal WASH and exocyst complexes control exocytosis of MT1-MMP at
invadopodia.
Monteiro P, Rossé C, Castro-Castro A, Irondelle M, Lagoutte E, Paul-Gilloteaux P,
Desnos C, Formstecher E, Darchen F, Perrais D, Gautreau A, Hertzog M, Chavrier P.
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: 10.1083/jcb.201306162
PMCID: PMC3871436
PMID: 24344185 [Indexed for MEDLINE]