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

Nom de la revue
Journal of Cell Biology
Pedro Monteiro, Carine Rossé, Antonio Castro-Castro, Marie Irondelle, Emilie Lagoutte, Perrine Paul-Gilloteaux, Claire Desnos, Etienne Formstecher, François Darchen, David Perrais, Alexis Gautreau, Maud Hertzog, Philippe Chavrier

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.