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Quantitative Measurement of Invadopodia-mediated Extracellular Matrix Proteolysis in Single and Multicellular Contexts
14:23

Quantitative Measurement of Invadopodia-mediated Extracellular Matrix Proteolysis in Single and Multicellular Contexts

Published on: August 27, 2012

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Endosomal WASH and exocyst complexes control exocytosis of MT1-MMP at invadopodia

Pedro Monteiro, Carine Rossé, Antonio Castro-Castro

    The Journal of Cell Biology
    |December 18, 2013
    PubMed

    Insights

    Tumor cells use the exocyst complex and WASH protein to deliver the enzyme MT1-MMP to invadopodia, enabling matrix degradation and cancer cell invasion through tissue. This process is crucial for metastatic dissemination.

    Area of Science:

    • Cell Biology
    • Cancer Research
    • Molecular Biology

    Background:

    • Metastatic dissemination involves extracellular matrix remodeling by carcinoma cells.
    • Invadopodia, actin-based protrusions, are essential for matrix degradation and accumulate type 1 matrix metalloproteinase (MT1-MMP).

    Purpose of the Study:

    • To investigate the interaction between the exocyst complex, WASH, and MT1-MMP in invasive breast carcinoma cells.
    • To elucidate the mechanism of MT1-MMP delivery for pericellular matrix degradation and tumor cell invasion.

    Main Methods:

    • Investigated the interaction of the exocyst complex and WASH on MT1-MMP–containing late endosomes.
    • Utilized microscopy and biochemical assays to study the exocytic mechanism of MT1-MMP delivery.

    Main Results:

    • Identified an interaction between the exocyst complex and WASH on MT1-MMP–containing late endosomes.
    • Demonstrated that WASH and exocyst are required for matrix degradation via tubular connections between endosomes and the plasma membrane.
    • Showcased focal delivery of MT1-MMP supporting pericellular matrix degradation and invasion.

    Conclusions:

    • A novel exocytic mechanism involving WASH and the exocyst complex facilitates MT1-MMP delivery to invadopodia.
    • This mechanism is critical for tumor cell invasion through basement membranes and collagen-rich tissues.
    • Suggests a general pathway for tumor cell invasion and metastasis.

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