RNAi-mediated knockdown of protein kinase C-alpha inhibits cell migration in MM-RU human metastatic melanoma cell line
Protein kinase C (PKC) is a multigene family of serine/threonine protein kinases involved in cell signaling pathways of proliferation and motility. PKC interacts with Rho GTPases in the regulation of the actin cytoskeleton. The PKC-alpha isozyme binds the Rho GTPase cdc42, and both are coordinated w...
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| Veröffentlicht in: | Melanoma research 2010-06, Vol.20 (3), p.171-178 |
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| creator | Byers, Hugh Randolph Boissel, Sandrine J S Tu, Chi Park, Hee-Young |
| description | Protein kinase C (PKC) is a multigene family of serine/threonine protein kinases involved in cell signaling pathways of proliferation and motility. PKC interacts with Rho GTPases in the regulation of the actin cytoskeleton. The PKC-alpha isozyme binds the Rho GTPase cdc42, and both are coordinated with the Rac-phosphatidylinositol-3 kinase (PI3K) signaling pathway in melanoma cell invasion and migration on extracellular matrix proteins. To further define the role of PKC-alpha in melanoma cell migration, we tested the effect of PDBu and Ca dependent activation of PKC-alpha as well as treatment with the PKC-alpha inhibitors calphostin C and Go6976. Furthermore, we transfected siRNA targeted against PKC-alpha into human melanoma cells and performed time-lapse analysis of cell migration followed by western immunoblotting. We found that significant enhancement of cell migration at 0.5 h after PDBu treatment directly correlated with Ca dependent activation of PKC-alpha and was inhibited by the PKC-alpha inhibitor calphostin C. PKC-alpha siRNA transfection nearly abrogated PKC-alpha expression and significantly reduced melanoma cell migration compared with siRNA controls. These findings provide further evidence that PKC-alpha plays an important role in melanoma cell migration and may have implications in therapies designed to disrupt melanoma cell motility by alteration of PKC-alpha signaling. |
| doi_str_mv | 10.1097/cmr.0b013e32832f1581 |
| format | Article |
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PKC-alpha siRNA transfection nearly abrogated PKC-alpha expression and significantly reduced melanoma cell migration compared with siRNA controls. 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PKC interacts with Rho GTPases in the regulation of the actin cytoskeleton. The PKC-alpha isozyme binds the Rho GTPase cdc42, and both are coordinated with the Rac-phosphatidylinositol-3 kinase (PI3K) signaling pathway in melanoma cell invasion and migration on extracellular matrix proteins. To further define the role of PKC-alpha in melanoma cell migration, we tested the effect of PDBu and Ca dependent activation of PKC-alpha as well as treatment with the PKC-alpha inhibitors calphostin C and Go6976. Furthermore, we transfected siRNA targeted against PKC-alpha into human melanoma cells and performed time-lapse analysis of cell migration followed by western immunoblotting. We found that significant enhancement of cell migration at 0.5 h after PDBu treatment directly correlated with Ca dependent activation of PKC-alpha and was inhibited by the PKC-alpha inhibitor calphostin C. PKC-alpha siRNA transfection nearly abrogated PKC-alpha expression and significantly reduced melanoma cell migration compared with siRNA controls. These findings provide further evidence that PKC-alpha plays an important role in melanoma cell migration and may have implications in therapies designed to disrupt melanoma cell motility by alteration of PKC-alpha signaling.</description><subject>Apoptosis</subject><subject>Carbazoles - pharmacology</subject><subject>cdc42 GTP-Binding Protein - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Extracellular Matrix - metabolism</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Melanoma - metabolism</subject><subject>Melanoma - pathology</subject><subject>Naphthalenes - pharmacology</subject><subject>Neoplasm Metastasis</subject><subject>Protein Isoforms</subject><subject>Protein Kinase C-alpha - genetics</subject><subject>Protein Kinase C-alpha - physiology</subject><subject>RNA Interference</subject><subject>Time Factors</subject><issn>0960-8931</issn><issn>1473-5636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUctO5DAQtNCuYHj8AUK-7SnQfsSxj2jEAhLDSiM4R7bTYcwkzhBnWO3fYzTAYS-cutVd1Y8qQk4ZnDMw1YXvx3NwwAQKrgVvWanZHpkxWYmiVEL9IDMwCgptBDsghyk9A7BKlGKfHHDgTDEQM_K6vL8MRY9NsBM2dB0Hv26Gv5EOLd2Mw4Qh0nWINiGdF7bbrCwNcRVcmBL12HW0D0-jncIQc50uFsXyka62vY20x8mmKbd8Tjsbh97uGF2IeEx-trZLePIRj8jj76uH-U1x9-f6dn55V3gJciqMAO65a5Qw4BouG9k6JRG5hso11iMzFXrtylJ7rRxvmJFKoMv_-9JpKY7Ir93c_MvLFtNU9yG9X2EjDttUV1JBFhPM90ghTJZWs4yUO6Qfh5RGbOvNGHo7_qsZ1O_W1PPFsv7fmkw7-1iwdVnvL9KnF-INjySLZg</recordid><startdate>201006</startdate><enddate>201006</enddate><creator>Byers, Hugh Randolph</creator><creator>Boissel, Sandrine J S</creator><creator>Tu, Chi</creator><creator>Park, Hee-Young</creator><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>7X8</scope><scope>7TM</scope></search><sort><creationdate>201006</creationdate><title>RNAi-mediated knockdown of protein kinase C-alpha inhibits cell migration in MM-RU human metastatic melanoma cell line</title><author>Byers, Hugh Randolph ; Boissel, Sandrine J S ; Tu, Chi ; Park, Hee-Young</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c404t-9302c2bd6390bd24d4fb64ee2807bdace197ec8b558c86b2d19463eb563c5b843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Apoptosis</topic><topic>Carbazoles - pharmacology</topic><topic>cdc42 GTP-Binding Protein - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Extracellular Matrix - metabolism</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Melanoma - metabolism</topic><topic>Melanoma - pathology</topic><topic>Naphthalenes - pharmacology</topic><topic>Neoplasm Metastasis</topic><topic>Protein Isoforms</topic><topic>Protein Kinase C-alpha - genetics</topic><topic>Protein Kinase C-alpha - physiology</topic><topic>RNA Interference</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Byers, Hugh Randolph</creatorcontrib><creatorcontrib>Boissel, Sandrine J S</creatorcontrib><creatorcontrib>Tu, Chi</creatorcontrib><creatorcontrib>Park, Hee-Young</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><jtitle>Melanoma research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Byers, Hugh Randolph</au><au>Boissel, Sandrine J S</au><au>Tu, Chi</au><au>Park, Hee-Young</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RNAi-mediated knockdown of protein kinase C-alpha inhibits cell migration in MM-RU human metastatic melanoma cell line</atitle><jtitle>Melanoma research</jtitle><addtitle>Melanoma Res</addtitle><date>2010-06</date><risdate>2010</risdate><volume>20</volume><issue>3</issue><spage>171</spage><epage>178</epage><pages>171-178</pages><issn>0960-8931</issn><eissn>1473-5636</eissn><abstract>Protein kinase C (PKC) is a multigene family of serine/threonine protein kinases involved in cell signaling pathways of proliferation and motility. PKC interacts with Rho GTPases in the regulation of the actin cytoskeleton. The PKC-alpha isozyme binds the Rho GTPase cdc42, and both are coordinated with the Rac-phosphatidylinositol-3 kinase (PI3K) signaling pathway in melanoma cell invasion and migration on extracellular matrix proteins. To further define the role of PKC-alpha in melanoma cell migration, we tested the effect of PDBu and Ca dependent activation of PKC-alpha as well as treatment with the PKC-alpha inhibitors calphostin C and Go6976. Furthermore, we transfected siRNA targeted against PKC-alpha into human melanoma cells and performed time-lapse analysis of cell migration followed by western immunoblotting. We found that significant enhancement of cell migration at 0.5 h after PDBu treatment directly correlated with Ca dependent activation of PKC-alpha and was inhibited by the PKC-alpha inhibitor calphostin C. 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| subjects | Apoptosis Carbazoles - pharmacology cdc42 GTP-Binding Protein - metabolism Cell Line, Tumor Cell Movement Extracellular Matrix - metabolism Gene Expression Regulation, Neoplastic Humans Melanoma - metabolism Melanoma - pathology Naphthalenes - pharmacology Neoplasm Metastasis Protein Isoforms Protein Kinase C-alpha - genetics Protein Kinase C-alpha - physiology RNA Interference Time Factors |
| title | RNAi-mediated knockdown of protein kinase C-alpha inhibits cell migration in MM-RU human metastatic melanoma cell line |
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