Endosomal WASH and exocyst complexes control exocytosis of MT1-MMP at invadopodia.
J Cell Biol
; 203(6): 1063-79, 2013 Dec 23.
Article
em En
| MEDLINE
| ID: mdl-24344185
ABSTRACT
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-MMPcontaining 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-MMPpositive 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte Vesicular
/
Exocitose
/
Proteínas dos Microfilamentos
Limite:
Female
/
Humans
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2013
Tipo de documento:
Article