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

[wiskott-aldrich syndrome]

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 (MT 1 -MMP ) accumulates . Here , we describe an interaction between the exocyst complex and the endosomal Arp 2 /3 activator Wiskott-Aldrich syndrome protein and Scar homolog (WASH ) on MT 1 -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 MT 1 -MMP–positive late endosomes and the plasma membrane in contact with the matrix . This ensures focal delivery of MT 1 -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 .