MT1-MMP-Dependent Invasion Is Regulated by TI-VAMP/VAMP7

• DOI: 10.1016/j.cub.2008.05.044
• Publication Date: 2008-06-20T08:14:05Z
• Authors: Anika Steffen; Gaëlle Le Dez; Renaud Poincloux; Chiara Recchi; Pierre Nassoy; Klemens Rottner; Thierry Galli; Philippe Chavrier
• Keywords: V-SNARES; MESH: Cell Line, Tumor; PERICELLULAR PROTEOLYSIS; MESH: R-SNARE Proteins; Breast Neoplasms; [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]; MESH: Extracellular Matrix; R-SNARE Proteins; MESH: Matrix Metalloproteinase 14; 03 medical and health sciences; Cell Line, Tumor; EXTRACELLULAR-MATRIX; [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]; Matrix Metalloproteinase 14; Humans; [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]; MATRIX-METALLOPROTEINASE MT1-MMP, TUMOR-CELL MIGRATION, PLASMA-MEMBRANE, EXTRACELLULAR-MATRIX, PERICELLULAR PROTEOLYSIS, EPITHELIAL-CELLS, V-SNARES, TI-VAMP, INVADOPODIA, DEGRADATION; 0303 health sciences; MESH: Humans; INVADOPODIA; Agricultural and Biological Sciences(all); Biochemistry, Genetics and Molecular Biology(all); MESH: Cell Surface Extensions; EPITHELIAL-CELLS; MESH: Gene Expression Regulation, Neoplastic; DEGRADATION; TUMOR-CELL MIGRATION; TI-VAMP; Extracellular Matrix; 3. Good health; Gene Expression Regulation, Neoplastic; PLASMA-MEMBRANE; [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]; CELLBIO; Cell Surface Extensions; MATRIX-METALLOPROTEINASE MT1-MMP; MESH: Breast Neoplasms

Proteolytic degradation of the extracellular matrix (ECM) is one intrinsic property of metastatic tumor cells to breach tissue barriers and to disseminate into different tissues. This process is initiated by the formation of invadopodia, which are actin-driven, finger-like membrane protrusions. Yet, little is known on how invadopodia are endowed with the functional machinery of proteolytic enzymes [1, 2]. The key protease MT1-MMP (membrane type 1-matrix metalloproteinase) confers proteolytic activity to invadopodia and thus invasion capacity of cancer cells [3-6]. Here, we report that MT1-MMP-dependent matrix degradation at invadopodia is regulated by the v-SNARE TI-VAMP/VAMP7, hence providing the molecular inventory mediating focal degradative activity of cancer cells. As observed by TIRF microscopy, MT1-MMP-mCherry and GFP-VAMP7 were simultaneously detected at proteolytic sites. Functional ablation of VAMP7 decreased the ability of breast cancer cells to degrade and invade in a MT1-MMP-dependent fashion. Moreover, the number of invadopodia was dramatically decreased in VAMP7- and MT1-MMP-depleted cells, indicative of a positive-feedback loop in which the protease as a cargo of VAMP7-targeted transport vesicles regulates maturation of invadopodia. Collectively, these data point to a specific role of VAMP7 in delivering MT1-MMP to sites of degradation, maintaining the functional machinery required for invasion.