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- Valentina Marchesin
- PSL Research University, Institut Curie, 75248 Paris, France 1
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- Antonio Castro-Castro
- PSL Research University, Institut Curie, 75248 Paris, France 1
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- Catalina Lodillinsky
- PSL Research University, Institut Curie, 75248 Paris, France 1
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- Alessia Castagnino
- PSL Research University, Institut Curie, 75248 Paris, France 1
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- Joanna Cyrta
- PSL Research University, Institut Curie, 75248 Paris, France 1
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- Hélène Bonsang-Kitzis
- Department of Translational Research, Residual Tumor and Response to Treatment Laboratory, Institut Curie, 75248 Paris, France 2
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- Laetitia Fuhrmann
- Department of Pathology, Institut Curie, 75248 Paris, France 5
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- Marie Irondelle
- PSL Research University, Institut Curie, 75248 Paris, France 1
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- Elvira Infante
- PSL Research University, Institut Curie, 75248 Paris, France 1
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- Guillaume Montagnac
- PSL Research University, Institut Curie, 75248 Paris, France 1
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- Fabien Reyal
- Department of Translational Research, Residual Tumor and Response to Treatment Laboratory, Institut Curie, 75248 Paris, France 2
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- Anne Vincent-Salomon
- Department of Pathology, Institut Curie, 75248 Paris, France 5
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- Philippe Chavrier
- PSL Research University, Institut Curie, 75248 Paris, France 1
書誌事項
- 公開日
- 2015-10-26
- DOI
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- 10.1083/jcb.201506002
- 公開者
- Rockefeller University Press
この論文をさがす
説明
<jats:p>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.</jats:p>
収録刊行物
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- Journal of Cell Biology
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Journal of Cell Biology 211 (2), 339-358, 2015-10-26
Rockefeller University Press