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. |