title: Endosomal WASH and exocyst complexes control exocytosis of MT1-MMP at invadopodia.
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-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.
authors.forename: Pedro
authors.initials: P
authors.lastname: Monteiro
authors.forename: Carine
authors.initials: C
authors.lastname: Rossé
authors.forename: Antonio
authors.initials: A
authors.lastname: Castro-Castro
authors.forename: Marie
authors.initials: M
authors.lastname: Irondelle
authors.forename: Emilie
authors.initials: E
authors.lastname: Lagoutte
authors.forename: Perrine
authors.initials: P
authors.lastname: Paul-Gilloteaux
authors.forename: Claire
authors.initials: C
authors.lastname: Desnos
authors.forename: Etienne
authors.initials: E
authors.lastname: Formstecher
authors.forename: François
authors.initials: F
authors.lastname: Darchen
authors.forename: David
authors.initials: D
authors.lastname: Perrais
authors.forename: Alexis
authors.initials: A
authors.lastname: Gautreau
authors.forename: Maud
authors.initials: M
authors.lastname: Hertzog
authors.forename: Philippe
authors.initials: P
authors.lastname: Chavrier
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology; D011992:Endosomes / Q000378:metabolism; D005089:Exocytosis; D005109:Extracellular Matrix / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000473:pathology / Q000648:ultrastructure; D033921:Vesicular Transport Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: D008840:Microfilament Proteins; D033921:Vesicular Transport Proteins; C549919:WASH protein, human; D053511:Matrix Metalloproteinase 14