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

• Published in: The Journal of cell biology Vol. 203; no. 6; pp. 1063 - 1079
• Main Authors: Monteiro, Pedro, Rossé, Carine, Castro-Castro, Antonio, Irondelle, Marie, Lagoutte, Emilie, Paul-Gilloteaux, Perrine, Desnos, Claire, Formstecher, Etienne, Darchen, François, Perrais, David, Gautreau, Alexis, Hertzog, Maud, Chavrier, Philippe
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 23.12.2013; The Rockefeller University Press
• Subjects: Adenocarcinoma - pathology; Breast cancer; Breast Neoplasms - pathology; Cells; Collagen; Endosomes - metabolism; Exocytosis; Extracellular Matrix - metabolism; Extracellular Matrix - ultrastructure; Female; Humans; Life Sciences; Matrix Metalloproteinase 14 - metabolism; Membranes; Microfilament Proteins - metabolism; Microfilament Proteins - physiology; Models, Biological; Neoplasm Invasiveness; Neoplasm Metastasis - pathology; Neoplasm Metastasis - ultrastructure; Proteins; Tissues; Tumors; Vesicular Transport Proteins - metabolism; Vesicular Transport Proteins - physiology
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201306162

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.