Protrudin-mediated ER-endosome contact sites promote MT1-MMP exocytosis and cell invasion.


Journal

The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356

Informations de publication

Date de publication:
03 08 2020
Historique:
received: 10 03 2020
revised: 04 05 2020
accepted: 05 05 2020
entrez: 2 6 2020
pubmed: 2 6 2020
medline: 23 3 2021
Statut: ppublish

Résumé

Cancer cells break tissue barriers by use of small actin-rich membrane protrusions called invadopodia. Complete invadopodia maturation depends on protrusion outgrowth and the targeted delivery of the matrix metalloproteinase MT1-MMP via endosomal transport by mechanisms that are not known. Here, we show that the ER protein Protrudin orchestrates invadopodia maturation and function. Protrudin formed contact sites with MT1-MMP-positive endosomes that contained the RAB7-binding Kinesin-1 adaptor FYCO1, and depletion of RAB7, FYCO1, or Protrudin inhibited MT1-MMP-dependent extracellular matrix degradation and cancer cell invasion by preventing anterograde translocation and exocytosis of MT1-MMP. Moreover, when endosome translocation or exocytosis was inhibited by depletion of Protrudin or Synaptotagmin VII, respectively, invadopodia were unable to expand and elongate. Conversely, when Protrudin was overexpressed, noncancerous cells developed prominent invadopodia-like protrusions and showed increased matrix degradation and invasion. Thus, Protrudin-mediated ER-endosome contact sites promote cell invasion by facilitating translocation of MT1-MMP-laden endosomes to the plasma membrane, enabling both invadopodia outgrowth and MT1-MMP exocytosis.

Identifiants

pubmed: 32479595
pii: 151827
doi: 10.1083/jcb.202003063
pmc: PMC7401796
pii:
doi:

Substances chimiques

FYCO1 protein, human 0
Microtubule-Associated Proteins 0
SYT7 protein, human 0
Vesicular Transport Proteins 0
ZFYVE27 protein, human 0
rab7 GTP-Binding Proteins 0
rab7 GTP-binding proteins, human 0
Synaptotagmins 134193-27-4
MMP14 protein, human EC 3.4.24.80
Matrix Metalloproteinase 14 EC 3.4.24.80
rab GTP-Binding Proteins EC 3.6.5.2

Types de publication

Journal Article Research Support, Non-U.S. Gov't Video-Audio Media

Langues

eng

Sous-ensembles de citation

IM

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2020 Pedersen et al.

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Auteurs

Nina Marie Pedersen (NM)

Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo, Norway.
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.

Eva Maria Wenzel (EM)

Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo, Norway.
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.

Ling Wang (L)

Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo, Norway.
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.

Sandra Antoine (S)

Research Center, Institut Curie, Membrane and Cytoskeleton Dynamics and Cell and Tissue Imaging Facility, Centre National de la Recherche Scientifique UMR 144, Paris, France.

Philippe Chavrier (P)

Research Center, Institut Curie, Membrane and Cytoskeleton Dynamics and Cell and Tissue Imaging Facility, Centre National de la Recherche Scientifique UMR 144, Paris, France.

Harald Stenmark (H)

Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo, Norway.
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.

Camilla Raiborg (C)

Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo, Norway.
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.

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