| The Wnt/planar cell polarity protein-tyrosine kinase-7 (PTK7) is a highly efficient proteolytic target of membrane type-1 matrix metalloproteinase: implications in cancer and embryogenesis. | |
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MedLine Citation:
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PMID: 20837484 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PTK7 is an essential component of the Wnt/planar cell polarity (PCP) pathway. We provide evidence that the Wnt/PCP pathway converges with pericellular proteolysis in both normal development and cancer. Here, we demonstrate that membrane type-1 matrix metalloproteinase (MT1-MMP), a key proinvasive proteinase, functions as a principal sheddase of PTK7. MT1-MMP directly cleaves the exposed PKP(621)↓LI sequence of the seventh Ig-like domain of the full-length membrane PTK7 and generates, as a result, an N-terminal, soluble PTK7 fragment (sPTK7). The enforced expression of membrane PTK7 in cancer cells leads to the actin cytoskeleton reorganization and the inhibition of cell invasion. MT1-MMP silencing and the analysis of the uncleavable L622D PTK7 mutant confirm the significance of MT1-MMP proteolysis of PTK7 in cell functions. Our data also demonstrate that a fine balance between the metalloproteinase activity and PTK7 levels is required for normal development of zebrafish (Danio rerio). Aberration of this balance by the proteinase inhibition or PTK7 silencing results in the PCP-dependent convergent extension defects in the zebrafish. Overall, our data suggest that the MT1-MMP-PTK7 axis plays an important role in both cancer cell invasion and normal embryogenesis in vertebrates. Further insight into these novel mechanisms may promote understanding of directional cell motility and lead to the identification of therapeutics to treat PCP-related developmental disorders and malignancy. |
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Authors:
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Vladislav S Golubkov; Alexei V Chekanov; Piotr Cieplak; Alexander E Aleshin; Andrei V Chernov; Wenhong Zhu; Ilian A Radichev; Danhua Zhang; P Duc Dong; Alex Y Strongin |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-09-13 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-08 Completed Date: 2011-02-09 Revised Date: 2013-05-28 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 35740-9 Citation Subset: IM |
Affiliation:
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Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GENBANK/GU211905 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Binding Sites / genetics Cell Adhesion Molecules / chemistry, genetics, metabolism* Cell Line Cell Line, Tumor Cell Movement Cell Polarity Cytoskeleton / metabolism Embryo, Nonmammalian / embryology*, metabolism Gene Expression Regulation, Developmental Gene Knockdown Techniques Humans In Situ Hybridization Matrix Metalloproteinase 14 / genetics, metabolism* Molecular Sequence Data Mutation Neoplasms / genetics, metabolism, pathology Protein Binding Protein Structure, Tertiary Receptor Protein-Tyrosine Kinases / chemistry, genetics, metabolism* Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Transfection Wnt Proteins / metabolism Zebrafish / embryology, genetics, metabolism Zebrafish Proteins / chemistry, genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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CA77470/CA/NCI NIH HHS; CA83017/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cell Adhesion Molecules; 0/Wnt Proteins; 0/Zebrafish Proteins; EC 2.7.1.-/PTK7 protein, human; EC 2.7.10.1/Receptor Protein-Tyrosine Kinases; EC 3.4.24.80/Matrix Metalloproteinase 14 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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