CCAR2/DBC1 and Hsp60 Positively Regulate Expression of Survivin in Neuroblastoma Cells
CCAR2 (cell cycle and apoptosis regulator 2) controls a variety of cellular functions; however, its main function is to regulate cell survival and cell death in response to genotoxic and metabolic stresses. Recently, we reported that CCAR2 protects cells from apoptosis following mitochondrial stress...
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description | CCAR2 (cell cycle and apoptosis regulator 2) controls a variety of cellular functions; however, its main function is to regulate cell survival and cell death in response to genotoxic and metabolic stresses. Recently, we reported that CCAR2 protects cells from apoptosis following mitochondrial stress, possibly by co-operating with Hsp60. However, it is not clear how CCAR2 and Hsp60 control cell survival and death. Here, we found that depleting CCAR2 and Hsp60 downregulated expression of survivin, a member of the inhibitor of apoptosis (IAP) family. Survivin expression in neuroblastoma tissues and human cancer cell lines correlated positively with expression of CCAR2 and Hsp60. Furthermore, high expression of CCAR2, Hsp60, and survivin was associated with poor survival of neuroblastoma patients. In summary, both CCAR2 and Hsp60 are required for expression of survivin, and both promote cancer cell survival, at least in part, by maintaining survivin expression. Therefore, CCAR2, Hsp60, and survivin are candidate tumor biomarkers and prognostic markers in neuroblastomas. |
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Recently, we reported that CCAR2 protects cells from apoptosis following mitochondrial stress, possibly by co-operating with Hsp60. However, it is not clear how CCAR2 and Hsp60 control cell survival and death. Here, we found that depleting CCAR2 and Hsp60 downregulated expression of survivin, a member of the inhibitor of apoptosis (IAP) family. Survivin expression in neuroblastoma tissues and human cancer cell lines correlated positively with expression of CCAR2 and Hsp60. Furthermore, high expression of CCAR2, Hsp60, and survivin was associated with poor survival of neuroblastoma patients. In summary, both CCAR2 and Hsp60 are required for expression of survivin, and both promote cancer cell survival, at least in part, by maintaining survivin expression. Therefore, CCAR2, Hsp60, and survivin are candidate tumor biomarkers and prognostic markers in neuroblastomas.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms20010131</identifier><identifier>PMID: 30609639</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Apoptosis ; Binding ; Cell cycle ; Cell death ; Depletion ; Hsp60 protein ; Mitochondria ; Neuroblastoma ; Neuroblasts ; Proteins ; Regulation ; Survival ; Survival factor ; Survivin</subject><ispartof>International journal of molecular sciences, 2019-01, Vol.20 (1), p.131</ispartof><rights>2019. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-84f93dec4f102db2cf2ba2ebc4fd0ed4b7f84b07e039c4b7bf7be01e220d95ab3</citedby><cites>FETCH-LOGICAL-c412t-84f93dec4f102db2cf2ba2ebc4fd0ed4b7f84b07e039c4b7bf7be01e220d95ab3</cites><orcidid>0000-0002-9132-1277</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337645/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337645/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30609639$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Wootae</creatorcontrib><creatorcontrib>Ryu, Jaewook</creatorcontrib><creatorcontrib>Kim, Ja-Eun</creatorcontrib><title>CCAR2/DBC1 and Hsp60 Positively Regulate Expression of Survivin in Neuroblastoma Cells</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>CCAR2 (cell cycle and apoptosis regulator 2) controls a variety of cellular functions; however, its main function is to regulate cell survival and cell death in response to genotoxic and metabolic stresses. 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Therefore, CCAR2, Hsp60, and survivin are candidate tumor biomarkers and prognostic markers in neuroblastomas.</description><subject>Apoptosis</subject><subject>Binding</subject><subject>Cell cycle</subject><subject>Cell death</subject><subject>Depletion</subject><subject>Hsp60 protein</subject><subject>Mitochondria</subject><subject>Neuroblastoma</subject><subject>Neuroblasts</subject><subject>Proteins</subject><subject>Regulation</subject><subject>Survival</subject><subject>Survival factor</subject><subject>Survivin</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkctLw0AQxhdRfFRvnmXBiwers48m5iLUWK0gKvVxXXaTiW5JsnU3Kfa_N2KVKizMzsyPj_n4CNlncCJEAqd2WgUOwIAJtka2meS8DxDF6yv_LbITwhSACz5INsmWgAiSSCTb5CVNhxN-enmRMqrrnI7DLAL64IJt7BzLBZ3ga1vqBunoY-YxBOtq6gr62Pq5nduadu8OW-9MqUPjKk1TLMuwSzYKXQbcW9Yeeb4aPaXj_u399U06vO1nkvGmfyaLROSYyYIBzw3PCm40R9MNcsBcmrg4kwZiBJFkXWeK2CAw5BzyZKCN6JHzb91ZayrMM6wbr0s187bSfqGcturvprZv6tXNVSREHMlBJ3C0FPDuvcXQqMqGrLOga3RtUJxFkoGMO75HDv-hU9f6urOnuBCcgQDxRR1_U5l3IXgsfo9hoL4CU6uBdfjBqoFf-Cch8Qna7pGt</recordid><startdate>20190101</startdate><enddate>20190101</enddate><creator>Kim, Wootae</creator><creator>Ryu, Jaewook</creator><creator>Kim, Ja-Eun</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9132-1277</orcidid></search><sort><creationdate>20190101</creationdate><title>CCAR2/DBC1 and Hsp60 Positively Regulate Expression of Survivin in Neuroblastoma Cells</title><author>Kim, Wootae ; Ryu, Jaewook ; Kim, Ja-Eun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-84f93dec4f102db2cf2ba2ebc4fd0ed4b7f84b07e039c4b7bf7be01e220d95ab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Apoptosis</topic><topic>Binding</topic><topic>Cell cycle</topic><topic>Cell death</topic><topic>Depletion</topic><topic>Hsp60 protein</topic><topic>Mitochondria</topic><topic>Neuroblastoma</topic><topic>Neuroblasts</topic><topic>Proteins</topic><topic>Regulation</topic><topic>Survival</topic><topic>Survival factor</topic><topic>Survivin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Wootae</creatorcontrib><creatorcontrib>Ryu, Jaewook</creatorcontrib><creatorcontrib>Kim, Ja-Eun</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</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 Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Wootae</au><au>Ryu, Jaewook</au><au>Kim, Ja-Eun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CCAR2/DBC1 and Hsp60 Positively Regulate Expression of Survivin in Neuroblastoma Cells</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2019-01-01</date><risdate>2019</risdate><volume>20</volume><issue>1</issue><spage>131</spage><pages>131-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>CCAR2 (cell cycle and apoptosis regulator 2) controls a variety of cellular functions; however, its main function is to regulate cell survival and cell death in response to genotoxic and metabolic stresses. Recently, we reported that CCAR2 protects cells from apoptosis following mitochondrial stress, possibly by co-operating with Hsp60. However, it is not clear how CCAR2 and Hsp60 control cell survival and death. Here, we found that depleting CCAR2 and Hsp60 downregulated expression of survivin, a member of the inhibitor of apoptosis (IAP) family. Survivin expression in neuroblastoma tissues and human cancer cell lines correlated positively with expression of CCAR2 and Hsp60. Furthermore, high expression of CCAR2, Hsp60, and survivin was associated with poor survival of neuroblastoma patients. In summary, both CCAR2 and Hsp60 are required for expression of survivin, and both promote cancer cell survival, at least in part, by maintaining survivin expression. 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subjects | Apoptosis Binding Cell cycle Cell death Depletion Hsp60 protein Mitochondria Neuroblastoma Neuroblasts Proteins Regulation Survival Survival factor Survivin |
title | CCAR2/DBC1 and Hsp60 Positively Regulate Expression of Survivin in Neuroblastoma Cells |
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