DOCK4, a GTPase Activator, Is Disrupted during Tumorigenesis
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 Ra...
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| Veröffentlicht in: | Cell 2003-03, Vol.112 (5), p.673-684 |
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| creator | Yajnik, Vijay Paulding, Charles Sordella, Raffaella McClatchey, Andrea I. Saito, Mako Wahrer, Doke C.R. Reynolds, Paul Bell, Daphne W. Lake, Robert van den Heuvel, Sander Settleman, Jeff Haber, Daniel A. |
| description | 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. |
| doi_str_mv | 10.1016/S0092-8674(03)00155-7 |
| format | Article |
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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.</description><identifier>ISSN: 0092-8674</identifier><identifier>EISSN: 1097-4172</identifier><identifier>DOI: 10.1016/S0092-8674(03)00155-7</identifier><identifier>PMID: 12628187</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Bone Neoplasms - genetics ; Bone Neoplasms - metabolism ; Caenorhabditis elegans ; Cell Transformation, Neoplastic - genetics ; Cell Transformation, Neoplastic - metabolism ; Eukaryotic Cells - metabolism ; Gene Deletion ; Gene Expression Regulation, Neoplastic - genetics ; Gene Expression Regulation, Neoplastic - physiology ; Gene Silencing - physiology ; Genes, Regulator - genetics ; GTPase-Activating Proteins - genetics ; GTPase-Activating Proteins - isolation & purification ; Homozygote ; Humans ; Mice ; Mice, Mutant Strains ; Molecular Sequence Data ; Mutation - genetics ; Osteosarcoma - genetics ; Osteosarcoma - metabolism ; rap GTP-Binding Proteins - genetics ; rap GTP-Binding Proteins - metabolism ; Sequence Homology, Amino Acid ; Sequence Homology, Nucleic Acid ; Tumor Cells, Cultured - enzymology</subject><ispartof>Cell, 2003-03, Vol.112 (5), p.673-684</ispartof><rights>2003 Cell Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c557t-7dbd905fb78af1c962943980029c19db3ab1ed69a059991e9afe93fe003186293</citedby><cites>FETCH-LOGICAL-c557t-7dbd905fb78af1c962943980029c19db3ab1ed69a059991e9afe93fe003186293</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0092867403001557$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12628187$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yajnik, Vijay</creatorcontrib><creatorcontrib>Paulding, Charles</creatorcontrib><creatorcontrib>Sordella, Raffaella</creatorcontrib><creatorcontrib>McClatchey, Andrea I.</creatorcontrib><creatorcontrib>Saito, Mako</creatorcontrib><creatorcontrib>Wahrer, Doke C.R.</creatorcontrib><creatorcontrib>Reynolds, Paul</creatorcontrib><creatorcontrib>Bell, Daphne W.</creatorcontrib><creatorcontrib>Lake, Robert</creatorcontrib><creatorcontrib>van den Heuvel, Sander</creatorcontrib><creatorcontrib>Settleman, Jeff</creatorcontrib><creatorcontrib>Haber, Daniel A.</creatorcontrib><title>DOCK4, a GTPase Activator, Is Disrupted during Tumorigenesis</title><title>Cell</title><addtitle>Cell</addtitle><description>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.</description><subject>Animals</subject><subject>Bone Neoplasms - genetics</subject><subject>Bone Neoplasms - metabolism</subject><subject>Caenorhabditis elegans</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Cell Transformation, Neoplastic - metabolism</subject><subject>Eukaryotic Cells - metabolism</subject><subject>Gene Deletion</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Gene Expression Regulation, Neoplastic - physiology</subject><subject>Gene Silencing - physiology</subject><subject>Genes, Regulator - genetics</subject><subject>GTPase-Activating Proteins - genetics</subject><subject>GTPase-Activating Proteins - isolation & purification</subject><subject>Homozygote</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Mutant Strains</subject><subject>Molecular Sequence Data</subject><subject>Mutation - genetics</subject><subject>Osteosarcoma - genetics</subject><subject>Osteosarcoma - metabolism</subject><subject>rap GTP-Binding Proteins - genetics</subject><subject>rap GTP-Binding Proteins - metabolism</subject><subject>Sequence Homology, Amino Acid</subject><subject>Sequence Homology, Nucleic Acid</subject><subject>Tumor Cells, Cultured - enzymology</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkF9LwzAUR4Mobk4_gtInUVj1pm2aBgQZm87hYILzOaTJrUTWdSbtwG9v9wd93NN9Off84BBySeGOAk3v3wFEFGYpT24gvgWgjIX8iHQpCB4mlEfHpPuHdMiZ918AkDHGTkmHRmmU0Yx3ycNoNnxN-oEKxvM35TEY6NquVV25fjDxwch616xqNIFpnF1-BvOmrJz9xCV668_JSaEWHi_2t0c-np_mw5dwOhtPhoNpqBnjdchNbgSwIueZKqgWaSSSWGQAkdBUmDxWOUWTCgVMCEFRqAJFXCBATLMWjnvkeuddueq7QV_L0nqNi4VaYtV4yWPIRJImB8FWJ1ojbUG2A7WrvHdYyJWzpXI_koLc9JXbvnITT0Ist33bnR652g80eYnm_2sftAUedwC2PdYWnfTa4lKjsQ51LU1lD0z8AtlQh58</recordid><startdate>20030307</startdate><enddate>20030307</enddate><creator>Yajnik, Vijay</creator><creator>Paulding, Charles</creator><creator>Sordella, Raffaella</creator><creator>McClatchey, Andrea I.</creator><creator>Saito, Mako</creator><creator>Wahrer, Doke C.R.</creator><creator>Reynolds, Paul</creator><creator>Bell, Daphne W.</creator><creator>Lake, Robert</creator><creator>van den Heuvel, Sander</creator><creator>Settleman, Jeff</creator><creator>Haber, Daniel A.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20030307</creationdate><title>DOCK4, a GTPase Activator, Is Disrupted during Tumorigenesis</title><author>Yajnik, Vijay ; Paulding, Charles ; Sordella, Raffaella ; McClatchey, Andrea I. ; Saito, Mako ; Wahrer, Doke C.R. ; Reynolds, Paul ; Bell, Daphne W. ; Lake, Robert ; van den Heuvel, Sander ; Settleman, Jeff ; Haber, Daniel A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c557t-7dbd905fb78af1c962943980029c19db3ab1ed69a059991e9afe93fe003186293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Bone Neoplasms - genetics</topic><topic>Bone Neoplasms - metabolism</topic><topic>Caenorhabditis elegans</topic><topic>Cell Transformation, Neoplastic - genetics</topic><topic>Cell Transformation, Neoplastic - metabolism</topic><topic>Eukaryotic Cells - metabolism</topic><topic>Gene Deletion</topic><topic>Gene Expression Regulation, Neoplastic - genetics</topic><topic>Gene Expression Regulation, Neoplastic - physiology</topic><topic>Gene Silencing - physiology</topic><topic>Genes, Regulator - genetics</topic><topic>GTPase-Activating Proteins - genetics</topic><topic>GTPase-Activating Proteins - isolation & purification</topic><topic>Homozygote</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Mutant Strains</topic><topic>Molecular Sequence Data</topic><topic>Mutation - genetics</topic><topic>Osteosarcoma - genetics</topic><topic>Osteosarcoma - metabolism</topic><topic>rap GTP-Binding Proteins - genetics</topic><topic>rap GTP-Binding Proteins - metabolism</topic><topic>Sequence Homology, Amino Acid</topic><topic>Sequence Homology, Nucleic Acid</topic><topic>Tumor Cells, Cultured - enzymology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yajnik, Vijay</creatorcontrib><creatorcontrib>Paulding, Charles</creatorcontrib><creatorcontrib>Sordella, Raffaella</creatorcontrib><creatorcontrib>McClatchey, Andrea I.</creatorcontrib><creatorcontrib>Saito, Mako</creatorcontrib><creatorcontrib>Wahrer, Doke C.R.</creatorcontrib><creatorcontrib>Reynolds, Paul</creatorcontrib><creatorcontrib>Bell, Daphne W.</creatorcontrib><creatorcontrib>Lake, Robert</creatorcontrib><creatorcontrib>van den Heuvel, Sander</creatorcontrib><creatorcontrib>Settleman, Jeff</creatorcontrib><creatorcontrib>Haber, Daniel A.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yajnik, Vijay</au><au>Paulding, Charles</au><au>Sordella, Raffaella</au><au>McClatchey, Andrea I.</au><au>Saito, Mako</au><au>Wahrer, Doke C.R.</au><au>Reynolds, Paul</au><au>Bell, Daphne W.</au><au>Lake, Robert</au><au>van den Heuvel, Sander</au><au>Settleman, Jeff</au><au>Haber, Daniel A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DOCK4, a GTPase Activator, Is Disrupted during Tumorigenesis</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>2003-03-07</date><risdate>2003</risdate><volume>112</volume><issue>5</issue><spage>673</spage><epage>684</epage><pages>673-684</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><abstract>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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>12628187</pmid><doi>10.1016/S0092-8674(03)00155-7</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Bone Neoplasms - genetics Bone Neoplasms - metabolism Caenorhabditis elegans Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - metabolism Eukaryotic Cells - metabolism Gene Deletion Gene Expression Regulation, Neoplastic - genetics Gene Expression Regulation, Neoplastic - physiology Gene Silencing - physiology Genes, Regulator - genetics GTPase-Activating Proteins - genetics GTPase-Activating Proteins - isolation & purification Homozygote Humans Mice Mice, Mutant Strains Molecular Sequence Data Mutation - genetics Osteosarcoma - genetics Osteosarcoma - metabolism rap GTP-Binding Proteins - genetics rap GTP-Binding Proteins - metabolism Sequence Homology, Amino Acid Sequence Homology, Nucleic Acid Tumor Cells, Cultured - enzymology |
| title | DOCK4, a GTPase Activator, Is Disrupted during Tumorigenesis |
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