Format

Send to

Choose Destination
J Cell Sci. 2018 Sep 5;131(17). pii: jcs218925. doi: 10.1242/jcs.218925.

MT1-MMP targeting to endolysosomes is mediated by upregulation of flotillins.

Author information

1
CRBM, Univ Montpellier, CNRS, France, 1919 Route de Mende, 34293 Montpellier, France.
2
Department of Genetics, Institut Curie, 75005 Paris, France.
3
Cancer Research Institute, Tomsk National Research Medical Center, Tomsk 634050, Russia.
4
Tomsk State University, Tomsk 634050, Russia.
5
Institut für Medizinische Mikrobiologie, Virologie und Hygiene, University Medical Center Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
6
Cell Dynamics and Compartmentalization Unit, Institut Curie, 75005 Paris, France.
7
CRBM, Univ Montpellier, CNRS, France, 1919 Route de Mende, 34293 Montpellier, France cecile.gauthier@crbm.cnrs.fr.

Abstract

Tumor cell invasion and metastasis formation are the major cause of death in cancer patients. These processes rely on extracellular matrix (ECM) degradation mediated by organelles termed invadopodia, to which the transmembrane matrix metalloproteinase MT1-MMP (also known as MMP14) is delivered from its reservoir, the RAB7-containing endolysosomes. How MT1-MMP is targeted to endolysosomes remains to be elucidated. Flotillin-1 and -2 are upregulated in many invasive cancers. Here, we show that flotillin upregulation triggers a general mechanism, common to carcinoma and sarcoma, which promotes RAB5-dependent MT1-MMP endocytosis and its delivery to RAB7-positive endolysosomal reservoirs. Conversely, flotillin knockdown in invasive cancer cells greatly reduces MT1-MMP accumulation in endolysosomes, its subsequent exocytosis at invadopodia, ECM degradation and cell invasion. Our results demonstrate that flotillin upregulation is necessary and sufficient to promote epithelial and mesenchymal cancer cell invasion and ECM degradation by controlling MT1-MMP endocytosis and delivery to the endolysosomal recycling compartment.

KEYWORDS:

Cancer cell invasion; Endolysosomal vesicular trafficking; Extracellular matrix degradation; Flotillin; MT1-MMP

PMID:
30111578
DOI:
10.1242/jcs.218925
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center