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

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.

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Phosphorylation of Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) and Its Vesicle-associated Membrane Protein 7 (VAMP7)-dependent Trafficking Facilitate Cell Invasion and Migration

Journal of Biological Chemistry ◽

10.1074/jbc.m111.297069 ◽

2011 ◽

Vol 286 (50) ◽

pp. 43405-43416 ◽

Cited By ~ 73

Author(s):

Karla C. Williams ◽

Marc G. Coppolino

Keyword(s):

Membrane Protein ◽

Matrix Metalloproteinase ◽

Cell Invasion ◽

Invasion And Migration ◽

Membrane Type ◽

And Migration

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Piezo1 mediates angiogenesis through activation of MT1-MMP signaling

AJP Cell Physiology ◽

10.1152/ajpcell.00346.2018 ◽

2019 ◽

Vol 316 (1) ◽

pp. C92-C103 ◽

Cited By ~ 19

Author(s):

Hojin Kang ◽

Zhigang Hong ◽

Ming Zhong ◽

Jennifer Klomp ◽

Kayla J. Bayless ◽

...

Keyword(s):

Shear Stress ◽

Wall Shear Stress ◽

Matrix Metalloproteinase ◽

Matrix Metalloproteinase 2 ◽

Sprouting Angiogenesis ◽

Sphingosine 1 Phosphate ◽

Wall Shear ◽

Membrane Type

Angiogenesis is initiated in response to a variety of external cues, including mechanical and biochemical stimuli; however, the underlying signaling mechanisms remain unclear. Here, we investigated the proangiogenic role of the endothelial mechanosensor Piezo1. Genetic deletion and pharmacological inhibition of Piezo1 reduced endothelial sprouting and lumen formation induced by wall shear stress and proangiogenic mediator sphingosine 1-phosphate, whereas Piezo1 activation by selective Piezo1 activator Yoda1 enhanced sprouting angiogenesis. Similarly to wall shear stress, sphingosine 1-phosphate functioned by activating the Ca2+ gating function of Piezo1, which in turn signaled the activation of the matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase during sprouting angiogenesis. Studies in mice in which Piezo1 was conditionally deleted in endothelial cells demonstrated the requisite role of sphingosine 1-phosphate-dependent activation of Piezo1 in mediating angiogenesis in vivo. These results taken together suggest that both mechanical and biochemical stimuli trigger Piezo1-mediated Ca2+ influx and thereby activate matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase and synergistically facilitate sprouting angiogenesis.

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