title: SNAP23, Syntaxin4, and vesicle-associated membrane protein 7 (VAMP7) mediate trafficking of membrane type 1-matrix metalloproteinase (MT1-MMP) during invadopodium formation and tumor cell invasion.
abstract: Movement through the extracellular matrix (ECM) requires cells to degrade ECM components, primarily through the action of matrix metalloproteinases (MMPs). Membrane type 1-matrix metalloproteinase (MT1-MMP) has an essential role in matrix degradation and cell invasion and localizes to subcellular degradative structures termed invadopodia. Trafficking of MT1-MMP to invadopodia is required for the function of these structures, and here we examine the role of N-ethylmaleimide-sensitive factor-activating protein receptor (SNARE)-mediated membrane traffic in the transport of MT1-MMP to invadopodia. During invadopodium formation in MDA-MB-231 human breast cancer cells, increased association of SNAP23, Syntaxin4, and vesicle-associated membrane protein 7 (VAMP7) is detected by coimmunoprecipitation. Blocking the function of these SNAREs perturbs invadopodium-based ECM degradation and cell invasion. Increased level of SNAP23-Syntaxin4-VAMP7 interaction correlates with decreased Syntaxin4 phosphorylation. These results reveal an important role for SNARE-regulated trafficking of MT1-MMP to invadopodia during cellular invasion of ECM.
authors.affiliation: Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada.
authors.forename: Karla C
authors.initials: KC
authors.lastname: Williams
authors.affiliation: Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada.
authors.forename: Rachael E
authors.initials: RE
authors.lastname: McNeilly
authors.affiliation: Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada mcoppoli@uoguelph.ca.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Coppolino
mesh_terms: D045744:Cell Line, Tumor; D022081:Cell Surface Extensions / Q000201:enzymology*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D021381:Protein Transport; D050765:Qa-SNARE Proteins / Q000378:metabolism*; D050766:Qb-SNARE Proteins / Q000378:metabolism*; D050767:Qc-SNARE Proteins / Q000378:metabolism*; D050683:R-SNARE Proteins / Q000378:metabolism*
chemical_list: D050765:Qa-SNARE Proteins; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D050683:R-SNARE Proteins; C100493:SNAP23 protein, human; C121241:VAMP7 protein, human; C587292:syntaxin 4, human; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14