Artículo
ARF6-JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasion
Marchesin, Valentina; Castro Castro, Antonio; Lodillinsky, Catalina
; Castagnino, Alessia; Cyrta, Joanna; Bonsang Kitzis, Hélène; Fuhrmann, Laetitia; Irondelle, Marie; Infante, Elvira; Montagnac, Guillaume; Reyal, Fabien; Vincent Salomon, Anne; Chavrier, Philippe
Fecha de publicación:
10/2015
Editorial:
Rockefeller University Press
Revista:
Journal of Cell Biology
ISSN:
0021-9525
e-ISSN:
1540-8140
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Invasion of cancer cells into collagen-rich extracellular matrix requires membrane-tethered membrane type 1-matrix metalloproteinase (MT1-MMP) as the key protease for collagen breakdown. Understanding how MT1-MMP is delivered to the surface of tumor cells is essential for cancer cell biology. In this study, we identify ARF6 together with c-Jun NH2-terminal kinase-interacting protein 3 and 4 (JIP3 and JIP4) effectors as critical regulators of this process. Silencing ARF6 or JIP3/JIP4 in breast tumor cells results in MT1-MMP endosome mispositioning and reduces MT1-MMP exocytosis and tumor cell invasion. JIPs are recruited by Wiskott-Aldrich syndrome protein and scar homologue (WASH) on MT1-MMP endosomes on which they recruit dynein-dynactin and kinesin-1. The interaction of plasma membrane ARF6 with endosomal JIPs coordinates dynactin-dynein and kinesin-1 activity in a tug-of-war mechanism, leading to MT1-MMP endosome tubulation and exocytosis. In addition, we find that ARF6, MT1-MMP, and kinesin-1 are up-regulated in high-grade triple-negative breast cancers. These data identify a critical ARF6-JIP-MT1-MMP-dynein-dynactin-kinesin-1 axis promoting an invasive phenotype of breast cancer cells.
Palabras clave:
Mt1-Mmp
,
Arf6
,
Breast Cancer
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Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Marchesin, Valentina; Castro Castro, Antonio; Lodillinsky, Catalina; Castagnino, Alessia; Cyrta, Joanna; et al.; ARF6-JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasion; Rockefeller University Press; Journal of Cell Biology; 211; 2; 10-2015; 339-358
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