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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2003-3-11
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pubmed:databankReference |
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pubmed:abstractText |
We used representational difference analysis to identify homozygous genomic deletions selected during tumor progression in the mouse NF2 and TP53 tumor model. We describe a deletion targeting DOCK4, a member of the CDM gene family encoding regulators of small GTPases. DOCK4 specifically activates Rap GTPase, enhancing the formation of adherens junctions. DOCK4 mutations are present in a subset of human cancer cell lines; a recurrent missense mutant identified in human prostate and ovarian cancers encodes a protein that is defective in Rap1 activation. The engulfment defect of C. elegans mutants lacking the CDM gene ced-5 is rescued by wild-type DOCK4, but not by the mutant allele. Expression of wild-type, but not mutant, DOCK4 in mouse osteosarcoma cells with a deletion of the endogenous gene suppresses growth in soft agar and tumor invasion in vivo. DOCK4 therefore encodes a CDM family member that regulates intercellular junctions and is disrupted during tumorigenesis.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0092-8674
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pubmed:author |
pubmed-author:BellDaphne WDW,
pubmed-author:HaberDaniel ADA,
pubmed-author:LakeRobertR,
pubmed-author:McClatcheyAndrea IAI,
pubmed-author:PauldingCharlesC,
pubmed-author:ReynoldsPaulP,
pubmed-author:SaitoMakoM,
pubmed-author:SettlemanJeffJ,
pubmed-author:SordellaRaffaellaR,
pubmed-author:WahrerDoke C RDC,
pubmed-author:YajnikVijayV,
pubmed-author:van den HeuvelSanderS
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
112
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
673-84
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12628187-Animals,
pubmed-meshheading:12628187-Bone Neoplasms,
pubmed-meshheading:12628187-Caenorhabditis elegans,
pubmed-meshheading:12628187-Cell Transformation, Neoplastic,
pubmed-meshheading:12628187-Eukaryotic Cells,
pubmed-meshheading:12628187-GTPase-Activating Proteins,
pubmed-meshheading:12628187-Gene Deletion,
pubmed-meshheading:12628187-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:12628187-Gene Silencing,
pubmed-meshheading:12628187-Genes, Regulator,
pubmed-meshheading:12628187-Homozygote,
pubmed-meshheading:12628187-Humans,
pubmed-meshheading:12628187-Mice,
pubmed-meshheading:12628187-Mice, Mutant Strains,
pubmed-meshheading:12628187-Molecular Sequence Data,
pubmed-meshheading:12628187-Mutation,
pubmed-meshheading:12628187-Osteosarcoma,
pubmed-meshheading:12628187-Sequence Homology, Amino Acid,
pubmed-meshheading:12628187-Sequence Homology, Nucleic Acid,
pubmed-meshheading:12628187-Tumor Cells, Cultured,
pubmed-meshheading:12628187-rap GTP-Binding Proteins
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pubmed:year |
2003
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pubmed:articleTitle |
DOCK4, a GTPase activator, is disrupted during tumorigenesis.
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pubmed:affiliation |
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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