Source:http://linkedlifedata.com/resource/pubmed/id/19934222
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
Pt 24
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pubmed:dateCreated |
2009-12-3
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pubmed:abstractText |
Complex signaling events control tumor invasion in three-dimensional (3D) extracellular matrices. Recent evidence suggests that cells utilize both matrix metalloproteinase (MMP)-dependent and MMP-independent means to traverse 3D matrices. Herein, we demonstrate that lysophosphatidic-acid-induced HT1080 cell invasion requires membrane-type-1 (MT1)-MMP-mediated collagenolysis to generate matrix conduits the width of a cellular nucleus. We define these spaces as single-cell invasion tunnels (SCITs). Once established, cells can migrate within SCITs in an MMP-independent manner. Endothelial cells, smooth muscle cells and fibroblasts also generate SCITs during invasive events, suggesting that SCIT formation represents a fundamental mechanism of cellular motility within 3D matrices. Coordinated cellular signaling events are required during SCIT formation. MT1-MMP, Cdc42 and its associated downstream effectors such as MRCK (myotonic dystrophy kinase-related Cdc42-binding kinase) and Pak4 (p21 protein-activated kinase 4), protein kinase Calpha and the Rho-associated coiled-coil-containing protein kinases (ROCK-1 and ROCK-2) coordinate signaling necessary for SCIT formation. Finally, we show that MT1-MMP and Cdc42 are fundamental components of a co-associated invasion-signaling complex that controls directed single-cell invasion of 3D collagen matrices.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1477-9137
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
122
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4558-69
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pubmed:dateRevised |
2011-5-10
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pubmed:meshHeading |
pubmed-meshheading:19934222-Cell Line, Tumor,
pubmed-meshheading:19934222-Cell Movement,
pubmed-meshheading:19934222-Collagen,
pubmed-meshheading:19934222-Extracellular Matrix,
pubmed-meshheading:19934222-Humans,
pubmed-meshheading:19934222-Matrix Metalloproteinase 14,
pubmed-meshheading:19934222-Models, Biological,
pubmed-meshheading:19934222-Neoplasm Invasiveness,
pubmed-meshheading:19934222-Neoplasms,
pubmed-meshheading:19934222-Signal Transduction,
pubmed-meshheading:19934222-cdc42 GTP-Binding Protein
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pubmed:year |
2009
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pubmed:articleTitle |
MT1-MMP- and Cdc42-dependent signaling co-regulate cell invasion and tunnel formation in 3D collagen matrices.
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pubmed:affiliation |
Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, MO 65212, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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