Phospholipase Cγ1 regulates the Rap GEF1-Rap1 signalling axis in the control of human prostate carcinoma cell adhesion
Phospholipase Cγ1 (PLCγ1) is activated downstream of a variety of extracellular stimuli and has previously been implicated in the regulation of motility responses central to tumour cell invasion. In this study, we used a novel RNAi vector system to achieve conditional PLCγ1 knockdown in PC3LN3 human...
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| Veröffentlicht in: | Oncogene 2008-05, Vol.27 (20), p.2823-2832 |
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| creator | Peak, J C Jones, N P Hobbs, S Katan, M Eccles, S A |
| description | Phospholipase Cγ1 (PLCγ1) is activated downstream of a variety of extracellular stimuli and has previously been implicated in the regulation of motility responses central to tumour cell invasion. In this study, we used a novel RNAi vector system to achieve conditional PLCγ1 knockdown in PC3LN3 human prostate carcinoma cells for further evaluation of PLCγ1 in tumour cell biology. Using this approach, we revealed a role for PLCγ1 in the regulation of PC3LN3 cell adhesion that appears to be independent of its effects on tumour cell chemotactic migration and spreading in response to extracellular matrix. Subsequent microarray analysis of PLCγ1-knockdown cells revealed Rap GEF1 mRNA to be decreased in response to PLCγ1 loss. This translated into a decrease in Rap GEF1 protein levels and a significant loss of Rap1 activity in PLCγ1-knockdown cells. Transient knockdown of Rap GEF1 caused a reduction in PC3LN3 adhesion while overexpression of Rap GEF1 rescued the PLCγ1 knockdown-induced adhesion defect. These data highlight control of the Rap GEF1–Rap1 molecular switch as a specific requirement for PLCγ1-mediated tumour cell adhesion. |
| doi_str_mv | 10.1038/sj.onc.1210954 |
| format | Article |
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In this study, we used a novel RNAi vector system to achieve conditional PLCγ1 knockdown in PC3LN3 human prostate carcinoma cells for further evaluation of PLCγ1 in tumour cell biology. Using this approach, we revealed a role for PLCγ1 in the regulation of PC3LN3 cell adhesion that appears to be independent of its effects on tumour cell chemotactic migration and spreading in response to extracellular matrix. Subsequent microarray analysis of PLCγ1-knockdown cells revealed Rap GEF1 mRNA to be decreased in response to PLCγ1 loss. This translated into a decrease in Rap GEF1 protein levels and a significant loss of Rap1 activity in PLCγ1-knockdown cells. Transient knockdown of Rap GEF1 caused a reduction in PC3LN3 adhesion while overexpression of Rap GEF1 rescued the PLCγ1 knockdown-induced adhesion defect. 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In this study, we used a novel RNAi vector system to achieve conditional PLCγ1 knockdown in PC3LN3 human prostate carcinoma cells for further evaluation of PLCγ1 in tumour cell biology. Using this approach, we revealed a role for PLCγ1 in the regulation of PC3LN3 cell adhesion that appears to be independent of its effects on tumour cell chemotactic migration and spreading in response to extracellular matrix. Subsequent microarray analysis of PLCγ1-knockdown cells revealed Rap GEF1 mRNA to be decreased in response to PLCγ1 loss. This translated into a decrease in Rap GEF1 protein levels and a significant loss of Rap1 activity in PLCγ1-knockdown cells. Transient knockdown of Rap GEF1 caused a reduction in PC3LN3 adhesion while overexpression of Rap GEF1 rescued the PLCγ1 knockdown-induced adhesion defect. These data highlight control of the Rap GEF1–Rap1 molecular switch as a specific requirement for PLCγ1-mediated tumour cell adhesion.</description><subject>Apoptosis</subject><subject>Care and treatment</subject><subject>Cell adhesion</subject><subject>Cell adhesion & migration</subject><subject>Cell Biology</subject><subject>Cellular signal transduction</subject><subject>Chemotaxis</subject><subject>Extracellular matrix</subject><subject>Genetic aspects</subject><subject>Human Genetics</subject><subject>Internal Medicine</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>mRNA</subject><subject>Oncology</subject><subject>original-article</subject><subject>Phospholipase C</subject><subject>Phospholipases</subject><subject>Physiological aspects</subject><subject>Prostate</subject><subject>Prostate cancer</subject><subject>Prostate carcinoma</subject><subject>Rap1 protein</subject><subject>RNA-mediated interference</subject><subject>Tumors</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kc9qHDEMxk1JoZu0154NPc-u7bHX42NYkrQQSCnt2Xg99owXjz2xZknyXHmPPlOdP5BLig4S4vcJSR9CXylZU9J2Gzisc7JryihRgn9AK8rlthFC8RO0qi3SKNayT-gU4EAIkYqwFbr7OWaYxxzDbMDh3d9HiosbjtEsDvAyOvzLzPjq4pI2taAYwpBMjCEN2NwHwCE9QzanpeSIs8fjcTIJzyXDUmdga4oNKU8GWxcjNv3oIOT0GX30JoL78prP0J_Li9-77831zdWP3fl1Y1mneOO9JXbPbNv30hPhJekk850Ue-kNE0I4Lym3bKtMpygTjDMm-j01fO_VtrXtGfr2MrcudHt0sOhDPpZ6Ami25bTtRNeJN2ow0emQfF6KsVMAq8-pIpIrKZ-o9TtUjd5NoX7A-VD77wls_QYU5_VcwmTKg6ZEP3mm4aCrZ_rVsyrYvAiggmlw5W3b_yj-AWxHmhY</recordid><startdate>20080501</startdate><enddate>20080501</enddate><creator>Peak, J C</creator><creator>Jones, N P</creator><creator>Hobbs, S</creator><creator>Katan, M</creator><creator>Eccles, S A</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope></search><sort><creationdate>20080501</creationdate><title>Phospholipase Cγ1 regulates the Rap GEF1-Rap1 signalling axis in the control of human prostate carcinoma cell adhesion</title><author>Peak, J C ; Jones, N P ; Hobbs, S ; Katan, M ; Eccles, S A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2894-ffc0cb2c3dd7f05f70872f875b7fa2555ef714c269a8912524225db1a4bf963c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Apoptosis</topic><topic>Care and treatment</topic><topic>Cell adhesion</topic><topic>Cell adhesion & migration</topic><topic>Cell Biology</topic><topic>Cellular signal transduction</topic><topic>Chemotaxis</topic><topic>Extracellular matrix</topic><topic>Genetic aspects</topic><topic>Human Genetics</topic><topic>Internal Medicine</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>mRNA</topic><topic>Oncology</topic><topic>original-article</topic><topic>Phospholipase C</topic><topic>Phospholipases</topic><topic>Physiological aspects</topic><topic>Prostate</topic><topic>Prostate cancer</topic><topic>Prostate carcinoma</topic><topic>Rap1 protein</topic><topic>RNA-mediated interference</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Peak, J C</creatorcontrib><creatorcontrib>Jones, N P</creatorcontrib><creatorcontrib>Hobbs, S</creatorcontrib><creatorcontrib>Katan, M</creatorcontrib><creatorcontrib>Eccles, S A</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Peak, J C</au><au>Jones, N P</au><au>Hobbs, S</au><au>Katan, M</au><au>Eccles, S A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phospholipase Cγ1 regulates the Rap GEF1-Rap1 signalling axis in the control of human prostate carcinoma cell adhesion</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><date>2008-05-01</date><risdate>2008</risdate><volume>27</volume><issue>20</issue><spage>2823</spage><epage>2832</epage><pages>2823-2832</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><abstract>Phospholipase Cγ1 (PLCγ1) is activated downstream of a variety of extracellular stimuli and has previously been implicated in the regulation of motility responses central to tumour cell invasion. In this study, we used a novel RNAi vector system to achieve conditional PLCγ1 knockdown in PC3LN3 human prostate carcinoma cells for further evaluation of PLCγ1 in tumour cell biology. Using this approach, we revealed a role for PLCγ1 in the regulation of PC3LN3 cell adhesion that appears to be independent of its effects on tumour cell chemotactic migration and spreading in response to extracellular matrix. Subsequent microarray analysis of PLCγ1-knockdown cells revealed Rap GEF1 mRNA to be decreased in response to PLCγ1 loss. This translated into a decrease in Rap GEF1 protein levels and a significant loss of Rap1 activity in PLCγ1-knockdown cells. Transient knockdown of Rap GEF1 caused a reduction in PC3LN3 adhesion while overexpression of Rap GEF1 rescued the PLCγ1 knockdown-induced adhesion defect. These data highlight control of the Rap GEF1–Rap1 molecular switch as a specific requirement for PLCγ1-mediated tumour cell adhesion.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><doi>10.1038/sj.onc.1210954</doi><tpages>10</tpages></addata></record> |
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| ispartof | Oncogene, 2008-05, Vol.27 (20), p.2823-2832 |
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| subjects | Apoptosis Care and treatment Cell adhesion Cell adhesion & migration Cell Biology Cellular signal transduction Chemotaxis Extracellular matrix Genetic aspects Human Genetics Internal Medicine Medicine Medicine & Public Health mRNA Oncology original-article Phospholipase C Phospholipases Physiological aspects Prostate Prostate cancer Prostate carcinoma Rap1 protein RNA-mediated interference Tumors |
| title | Phospholipase Cγ1 regulates the Rap GEF1-Rap1 signalling axis in the control of human prostate carcinoma cell adhesion |
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