Inhibition of TASK-3 (KCNK9) channel biosynthesis changes cell morphology and decreases both DNA content and mitochondrial function of melanoma cells maintained in cell culture
TASK-3 channel overexpression was shown to facilitate the survival of malignantly transformed cells, possibly by providing greater hypoxia tolerance through a still unknown mechanism. Although it has been suggested previously that TASK-3 channels are expressed in the mitochondrial membranes, their r...
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Veröffentlicht in: | Melanoma research 2011-08, Vol.21 (4), p.308-322 |
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creator | Kosztka, Lívia Rusznák, Zoltán Nagy, Dénes Nagy, Zsuzsanna Fodor, János Szucs, Géza Telek, Andrea Gönczi, Mónika Ruzsnavszky, Olga Szentandrássy, Norbert Csernoch, László |
description | TASK-3 channel overexpression was shown to facilitate the survival of malignantly transformed cells, possibly by providing greater hypoxia tolerance through a still unknown mechanism. Although it has been suggested previously that TASK-3 channels are expressed in the mitochondrial membranes, their role here remains elusive. In this study, a transient transfection of TASK-3 knockdown melanoma cell cultures was produced to show the significance of TASK-3 expression. Reduction of the TASK-3 protein biosynthesis induced characteristic changes in cell morphology, reduced the amount of DNA and decreased metabolic activity and mitochondrial function of melanoma cells when compared with control. These findings indicate that TASK-3 channel expression and function is indispensable for the proliferation and/or survival of the melanoma cells, as they seem to contribute to their mitochondrial functions. The significance is that, in this study, we have shown that TASK-3 channels are expressed in the mitochondria of melanoma malignum cells, and they are essential for maintaining cellular integrity and viability. The TASK-3 knockdown melanoma cell line had altered morphology, reduced DNA content, decreased metabolic activity and impaired mitochondrial function. These data indicate that TASK-3 channels are functionally present in the mitochondria of the melanoma cells, and their function is essential for the survival of these cells, thus TASK-3 channels may be the possible targets of future anticancer therapy. |
doi_str_mv | 10.1097/CMR.0b013e3283462713 |
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Although it has been suggested previously that TASK-3 channels are expressed in the mitochondrial membranes, their role here remains elusive. In this study, a transient transfection of TASK-3 knockdown melanoma cell cultures was produced to show the significance of TASK-3 expression. Reduction of the TASK-3 protein biosynthesis induced characteristic changes in cell morphology, reduced the amount of DNA and decreased metabolic activity and mitochondrial function of melanoma cells when compared with control. These findings indicate that TASK-3 channel expression and function is indispensable for the proliferation and/or survival of the melanoma cells, as they seem to contribute to their mitochondrial functions. The significance is that, in this study, we have shown that TASK-3 channels are expressed in the mitochondria of melanoma malignum cells, and they are essential for maintaining cellular integrity and viability. The TASK-3 knockdown melanoma cell line had altered morphology, reduced DNA content, decreased metabolic activity and impaired mitochondrial function. These data indicate that TASK-3 channels are functionally present in the mitochondria of the melanoma cells, and their function is essential for the survival of these cells, thus TASK-3 channels may be the possible targets of future anticancer therapy.</description><identifier>ISSN: 0960-8931</identifier><identifier>EISSN: 1473-5636</identifier><identifier>DOI: 10.1097/CMR.0b013e3283462713</identifier><identifier>PMID: 21512417</identifier><language>eng</language><publisher>England</publisher><subject>Cell Line, Tumor ; Cell Proliferation ; Cell Shape ; Cell Size ; Cell Survival ; DNA - metabolism ; Energy Metabolism ; HEK293 Cells ; Humans ; Melanoma - genetics ; Melanoma - metabolism ; Melanoma - pathology ; Mitochondria - metabolism ; Mitochondria - pathology ; Potassium Channels, Tandem Pore Domain - biosynthesis ; Potassium Channels, Tandem Pore Domain - genetics ; RNA Interference ; Time Factors ; Transfection</subject><ispartof>Melanoma research, 2011-08, Vol.21 (4), p.308-322</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c338t-58c15354d4815c1a07f39fa9fbc254c7ce39ce4b34f2fb5331d479a3dff214053</citedby><cites>FETCH-LOGICAL-c338t-58c15354d4815c1a07f39fa9fbc254c7ce39ce4b34f2fb5331d479a3dff214053</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21512417$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kosztka, Lívia</creatorcontrib><creatorcontrib>Rusznák, Zoltán</creatorcontrib><creatorcontrib>Nagy, Dénes</creatorcontrib><creatorcontrib>Nagy, Zsuzsanna</creatorcontrib><creatorcontrib>Fodor, János</creatorcontrib><creatorcontrib>Szucs, Géza</creatorcontrib><creatorcontrib>Telek, Andrea</creatorcontrib><creatorcontrib>Gönczi, Mónika</creatorcontrib><creatorcontrib>Ruzsnavszky, Olga</creatorcontrib><creatorcontrib>Szentandrássy, Norbert</creatorcontrib><creatorcontrib>Csernoch, László</creatorcontrib><title>Inhibition of TASK-3 (KCNK9) channel biosynthesis changes cell morphology and decreases both DNA content and mitochondrial function of melanoma cells maintained in cell culture</title><title>Melanoma research</title><addtitle>Melanoma Res</addtitle><description>TASK-3 channel overexpression was shown to facilitate the survival of malignantly transformed cells, possibly by providing greater hypoxia tolerance through a still unknown mechanism. Although it has been suggested previously that TASK-3 channels are expressed in the mitochondrial membranes, their role here remains elusive. In this study, a transient transfection of TASK-3 knockdown melanoma cell cultures was produced to show the significance of TASK-3 expression. Reduction of the TASK-3 protein biosynthesis induced characteristic changes in cell morphology, reduced the amount of DNA and decreased metabolic activity and mitochondrial function of melanoma cells when compared with control. These findings indicate that TASK-3 channel expression and function is indispensable for the proliferation and/or survival of the melanoma cells, as they seem to contribute to their mitochondrial functions. The significance is that, in this study, we have shown that TASK-3 channels are expressed in the mitochondria of melanoma malignum cells, and they are essential for maintaining cellular integrity and viability. The TASK-3 knockdown melanoma cell line had altered morphology, reduced DNA content, decreased metabolic activity and impaired mitochondrial function. These data indicate that TASK-3 channels are functionally present in the mitochondria of the melanoma cells, and their function is essential for the survival of these cells, thus TASK-3 channels may be the possible targets of future anticancer therapy.</description><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cell Shape</subject><subject>Cell Size</subject><subject>Cell Survival</subject><subject>DNA - metabolism</subject><subject>Energy Metabolism</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Melanoma - genetics</subject><subject>Melanoma - metabolism</subject><subject>Melanoma - pathology</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondria - pathology</subject><subject>Potassium Channels, Tandem Pore Domain - biosynthesis</subject><subject>Potassium Channels, Tandem Pore Domain - genetics</subject><subject>RNA Interference</subject><subject>Time Factors</subject><subject>Transfection</subject><issn>0960-8931</issn><issn>1473-5636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUcFu1DAQtRAV3S78AUK-0R5S7Iy9to-rpUC1pUhQzpHj2I1RYi-2c9i_4hNJd1sOvXAYPWnem3mjeQi9peSSEiU-bL5-vyQtoWChlsBWtaDwAi0oE1DxFaxeogVRK1JJBfQUneX8ixAqgMMrdFpTTmtGxQL9uQ69b33xMeDo8N36x7YCfL7d3G7VBTa9DsEOuPUx70Ppbfb50Ly3M9phwGNMuz4O8X6PdehwZ02yOs9sG0uPP96usYmh2FAO9OhLNH0MXfJ6wG4K5sl4tIMOcdSHrRmP2ocyl-2wD0cnMw1lSvY1OnF6yPbNIy7Rz09Xd5sv1c23z9eb9U1lAGSpuDSUA2cdk5QbqolwoJxWrjU1Z0YYC8pY1gJztWs5AO2YUBo652rKCIclen_cu0vx92RzaUafHw7RwcYpN4oIKpiU5L9KKTnhXM6_XyJ2VJoUc07WNbvkR532DSXNQ6jNHGrzPNR57N2jwdSOtvs39JQi_AVaop-s</recordid><startdate>201108</startdate><enddate>201108</enddate><creator>Kosztka, Lívia</creator><creator>Rusznák, Zoltán</creator><creator>Nagy, Dénes</creator><creator>Nagy, Zsuzsanna</creator><creator>Fodor, János</creator><creator>Szucs, Géza</creator><creator>Telek, Andrea</creator><creator>Gönczi, Mónika</creator><creator>Ruzsnavszky, Olga</creator><creator>Szentandrássy, Norbert</creator><creator>Csernoch, László</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>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>201108</creationdate><title>Inhibition of TASK-3 (KCNK9) channel biosynthesis changes cell morphology and decreases both DNA content and mitochondrial function of melanoma cells maintained in cell culture</title><author>Kosztka, Lívia ; 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Although it has been suggested previously that TASK-3 channels are expressed in the mitochondrial membranes, their role here remains elusive. In this study, a transient transfection of TASK-3 knockdown melanoma cell cultures was produced to show the significance of TASK-3 expression. Reduction of the TASK-3 protein biosynthesis induced characteristic changes in cell morphology, reduced the amount of DNA and decreased metabolic activity and mitochondrial function of melanoma cells when compared with control. These findings indicate that TASK-3 channel expression and function is indispensable for the proliferation and/or survival of the melanoma cells, as they seem to contribute to their mitochondrial functions. The significance is that, in this study, we have shown that TASK-3 channels are expressed in the mitochondria of melanoma malignum cells, and they are essential for maintaining cellular integrity and viability. 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subjects | Cell Line, Tumor Cell Proliferation Cell Shape Cell Size Cell Survival DNA - metabolism Energy Metabolism HEK293 Cells Humans Melanoma - genetics Melanoma - metabolism Melanoma - pathology Mitochondria - metabolism Mitochondria - pathology Potassium Channels, Tandem Pore Domain - biosynthesis Potassium Channels, Tandem Pore Domain - genetics RNA Interference Time Factors Transfection |
title | Inhibition of TASK-3 (KCNK9) channel biosynthesis changes cell morphology and decreases both DNA content and mitochondrial function of melanoma cells maintained in cell culture |
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