Cytoglobin ameliorates the stemness of hepatocellular carcinoma via coupling oxidative‐nitrosative stress signals
Cancer stem cells (CSCs) account for tumor self‐renewal and heterogeneity. Oxidative‐nitrosative stress (ONS) is an independent etiologic factor throughout tumorigenesis. Emerging evidences indicated that the interaction of ONS with CSCs contributes to tumor progression and resistance to chemoradiot...
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| Veröffentlicht in: | Molecular carcinogenesis 2019-03, Vol.58 (3), p.334-343 |
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| creator | Zhang, Jun Pei, YuanYuan Yang, Wen Yang, WenXiu Chen, BoXin Zhao, Xing Long, Shiqi |
| description | Cancer stem cells (CSCs) account for tumor self‐renewal and heterogeneity. Oxidative‐nitrosative stress (ONS) is an independent etiologic factor throughout tumorigenesis. Emerging evidences indicated that the interaction of ONS with CSCs contributes to tumor progression and resistance to chemoradiotherapy. Cytoglobin (Cygb) is a member of human hexacoordinate hemoglobin family and acts as a dynamic mediator of redox homeostasis. We observed that Cygb is significantly deregulated in human hepatocellular carcinoma (HCC) tissue and its decrease aggravates the growth of liver cancer stem cells (LCSCs) and increases the subpopulation of CD133(+) LCSCs. Cygb restoration inhibits HCC proliferation and LCSC growth, and decreases the subpopulation of CD133 (+) LCSCs in vitro. We found that Cygb absence promotes LCSC phenotypes and PI3 K/AKT activation, whereas Cygb restoration inhibits LCSC phenotypes and PI3 K/AKT activation. Furthermore, exogenous antioxidants can eliminate the inhibitory effect of Cygb to LCSC growth and phenotypes, as well as PI3 K/AKT activation. Collectively, this study demonstrated that cytoglobin functions as a tumor suppressor and targets CSCs at an ONS‐dependent manner. Thus, Cygb restoration could be a novel and promising therapeutic strategy against HCC with aberrant ROS/RNS accumulation. |
| doi_str_mv | 10.1002/mc.22931 |
| format | Article |
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Oxidative‐nitrosative stress (ONS) is an independent etiologic factor throughout tumorigenesis. Emerging evidences indicated that the interaction of ONS with CSCs contributes to tumor progression and resistance to chemoradiotherapy. Cytoglobin (Cygb) is a member of human hexacoordinate hemoglobin family and acts as a dynamic mediator of redox homeostasis. We observed that Cygb is significantly deregulated in human hepatocellular carcinoma (HCC) tissue and its decrease aggravates the growth of liver cancer stem cells (LCSCs) and increases the subpopulation of CD133(+) LCSCs. Cygb restoration inhibits HCC proliferation and LCSC growth, and decreases the subpopulation of CD133 (+) LCSCs in vitro. We found that Cygb absence promotes LCSC phenotypes and PI3 K/AKT activation, whereas Cygb restoration inhibits LCSC phenotypes and PI3 K/AKT activation. Furthermore, exogenous antioxidants can eliminate the inhibitory effect of Cygb to LCSC growth and phenotypes, as well as PI3 K/AKT activation. Collectively, this study demonstrated that cytoglobin functions as a tumor suppressor and targets CSCs at an ONS‐dependent manner. Thus, Cygb restoration could be a novel and promising therapeutic strategy against HCC with aberrant ROS/RNS accumulation.</description><identifier>ISSN: 0899-1987</identifier><identifier>EISSN: 1098-2744</identifier><identifier>DOI: 10.1002/mc.22931</identifier><identifier>PMID: 30365183</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Activation ; AKT protein ; Antioxidants ; Cell self-renewal ; Chemoradiotherapy ; cytoglobin ; Hemoglobin ; Hepatocellular carcinoma ; Hepatocytes ; Heterogeneity ; Homeostasis ; Liver ; Liver cancer ; liver cancer stem cells ; oxidative‐nitrosative stress ; Phenotypes ; PI3 K/AKT signal ; Reactive oxygen species ; Stem cells ; Tumor suppressor genes ; Tumorigenesis</subject><ispartof>Molecular carcinogenesis, 2019-03, Vol.58 (3), p.334-343</ispartof><rights>2018 Wiley Periodicals, Inc.</rights><rights>2019 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4151-b35ac842e4323a8cf19583b945371ef440fe36c8c74c36404d973e5145d23f923</citedby><cites>FETCH-LOGICAL-c4151-b35ac842e4323a8cf19583b945371ef440fe36c8c74c36404d973e5145d23f923</cites><orcidid>0000-0002-7453-748X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmc.22931$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmc.22931$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30365183$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Jun</creatorcontrib><creatorcontrib>Pei, YuanYuan</creatorcontrib><creatorcontrib>Yang, Wen</creatorcontrib><creatorcontrib>Yang, WenXiu</creatorcontrib><creatorcontrib>Chen, BoXin</creatorcontrib><creatorcontrib>Zhao, Xing</creatorcontrib><creatorcontrib>Long, Shiqi</creatorcontrib><title>Cytoglobin ameliorates the stemness of hepatocellular carcinoma via coupling oxidative‐nitrosative stress signals</title><title>Molecular carcinogenesis</title><addtitle>Mol Carcinog</addtitle><description>Cancer stem cells (CSCs) account for tumor self‐renewal and heterogeneity. Oxidative‐nitrosative stress (ONS) is an independent etiologic factor throughout tumorigenesis. Emerging evidences indicated that the interaction of ONS with CSCs contributes to tumor progression and resistance to chemoradiotherapy. Cytoglobin (Cygb) is a member of human hexacoordinate hemoglobin family and acts as a dynamic mediator of redox homeostasis. We observed that Cygb is significantly deregulated in human hepatocellular carcinoma (HCC) tissue and its decrease aggravates the growth of liver cancer stem cells (LCSCs) and increases the subpopulation of CD133(+) LCSCs. Cygb restoration inhibits HCC proliferation and LCSC growth, and decreases the subpopulation of CD133 (+) LCSCs in vitro. We found that Cygb absence promotes LCSC phenotypes and PI3 K/AKT activation, whereas Cygb restoration inhibits LCSC phenotypes and PI3 K/AKT activation. Furthermore, exogenous antioxidants can eliminate the inhibitory effect of Cygb to LCSC growth and phenotypes, as well as PI3 K/AKT activation. Collectively, this study demonstrated that cytoglobin functions as a tumor suppressor and targets CSCs at an ONS‐dependent manner. Thus, Cygb restoration could be a novel and promising therapeutic strategy against HCC with aberrant ROS/RNS accumulation.</description><subject>Activation</subject><subject>AKT protein</subject><subject>Antioxidants</subject><subject>Cell self-renewal</subject><subject>Chemoradiotherapy</subject><subject>cytoglobin</subject><subject>Hemoglobin</subject><subject>Hepatocellular carcinoma</subject><subject>Hepatocytes</subject><subject>Heterogeneity</subject><subject>Homeostasis</subject><subject>Liver</subject><subject>Liver cancer</subject><subject>liver cancer stem cells</subject><subject>oxidative‐nitrosative stress</subject><subject>Phenotypes</subject><subject>PI3 K/AKT signal</subject><subject>Reactive oxygen species</subject><subject>Stem cells</subject><subject>Tumor suppressor genes</subject><subject>Tumorigenesis</subject><issn>0899-1987</issn><issn>1098-2744</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kctKAzEUhoMoWi_gE0jAjZupObl0kqUUb6C40fWQpmdqZGZSkxm1Ox_BZ_RJnFovILg6HPj4OP_5CdkHNgTG-HHthpwbAWtkAMzojOdSrpMB08ZkYHS-RbZTemAMIFdsk2wJJkYKtBiQNF60YVaFiW-orbHyIdoWE23vkaYW6wZToqGk9zi3bXBYVV1lI3U2Ot-E2tInb6kL3bzyzYyGFz-1rX_C99e3xrcxpM-tN8WlJ_lZY6u0SzbKfuDe19whd2ent-OL7Orm_HJ8cpU5CQqyiVDWaclRCi6sdiUYpcXESCVywFJKVqIYOe1y6cRIMjk1uUAFUk25KA0XO-Ro5Z3H8Nhhaovap2UE22DoUsGBjwxjOagePfyDPoQuLo_tqVyC4VqbX6Hrk6WIZTGPvrZxUQArlkUUtSs-i-jRgy9hN6lx-gN-f74HshXw7Ctc_Csqrscr4Qe8g5Lz</recordid><startdate>201903</startdate><enddate>201903</enddate><creator>Zhang, Jun</creator><creator>Pei, YuanYuan</creator><creator>Yang, Wen</creator><creator>Yang, WenXiu</creator><creator>Chen, BoXin</creator><creator>Zhao, Xing</creator><creator>Long, Shiqi</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7453-748X</orcidid></search><sort><creationdate>201903</creationdate><title>Cytoglobin ameliorates the stemness of hepatocellular carcinoma via coupling oxidative‐nitrosative stress signals</title><author>Zhang, Jun ; Pei, YuanYuan ; Yang, Wen ; Yang, WenXiu ; Chen, BoXin ; Zhao, Xing ; Long, Shiqi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4151-b35ac842e4323a8cf19583b945371ef440fe36c8c74c36404d973e5145d23f923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Activation</topic><topic>AKT protein</topic><topic>Antioxidants</topic><topic>Cell self-renewal</topic><topic>Chemoradiotherapy</topic><topic>cytoglobin</topic><topic>Hemoglobin</topic><topic>Hepatocellular carcinoma</topic><topic>Hepatocytes</topic><topic>Heterogeneity</topic><topic>Homeostasis</topic><topic>Liver</topic><topic>Liver cancer</topic><topic>liver cancer stem cells</topic><topic>oxidative‐nitrosative stress</topic><topic>Phenotypes</topic><topic>PI3 K/AKT signal</topic><topic>Reactive oxygen species</topic><topic>Stem cells</topic><topic>Tumor suppressor genes</topic><topic>Tumorigenesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Jun</creatorcontrib><creatorcontrib>Pei, YuanYuan</creatorcontrib><creatorcontrib>Yang, Wen</creatorcontrib><creatorcontrib>Yang, WenXiu</creatorcontrib><creatorcontrib>Chen, BoXin</creatorcontrib><creatorcontrib>Zhao, Xing</creatorcontrib><creatorcontrib>Long, Shiqi</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</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>Molecular carcinogenesis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Jun</au><au>Pei, YuanYuan</au><au>Yang, Wen</au><au>Yang, WenXiu</au><au>Chen, BoXin</au><au>Zhao, Xing</au><au>Long, Shiqi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytoglobin ameliorates the stemness of hepatocellular carcinoma via coupling oxidative‐nitrosative stress signals</atitle><jtitle>Molecular carcinogenesis</jtitle><addtitle>Mol Carcinog</addtitle><date>2019-03</date><risdate>2019</risdate><volume>58</volume><issue>3</issue><spage>334</spage><epage>343</epage><pages>334-343</pages><issn>0899-1987</issn><eissn>1098-2744</eissn><abstract>Cancer stem cells (CSCs) account for tumor self‐renewal and heterogeneity. Oxidative‐nitrosative stress (ONS) is an independent etiologic factor throughout tumorigenesis. Emerging evidences indicated that the interaction of ONS with CSCs contributes to tumor progression and resistance to chemoradiotherapy. Cytoglobin (Cygb) is a member of human hexacoordinate hemoglobin family and acts as a dynamic mediator of redox homeostasis. We observed that Cygb is significantly deregulated in human hepatocellular carcinoma (HCC) tissue and its decrease aggravates the growth of liver cancer stem cells (LCSCs) and increases the subpopulation of CD133(+) LCSCs. Cygb restoration inhibits HCC proliferation and LCSC growth, and decreases the subpopulation of CD133 (+) LCSCs in vitro. We found that Cygb absence promotes LCSC phenotypes and PI3 K/AKT activation, whereas Cygb restoration inhibits LCSC phenotypes and PI3 K/AKT activation. Furthermore, exogenous antioxidants can eliminate the inhibitory effect of Cygb to LCSC growth and phenotypes, as well as PI3 K/AKT activation. Collectively, this study demonstrated that cytoglobin functions as a tumor suppressor and targets CSCs at an ONS‐dependent manner. Thus, Cygb restoration could be a novel and promising therapeutic strategy against HCC with aberrant ROS/RNS accumulation.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30365183</pmid><doi>10.1002/mc.22931</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-7453-748X</orcidid></addata></record> |
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| subjects | Activation AKT protein Antioxidants Cell self-renewal Chemoradiotherapy cytoglobin Hemoglobin Hepatocellular carcinoma Hepatocytes Heterogeneity Homeostasis Liver Liver cancer liver cancer stem cells oxidative‐nitrosative stress Phenotypes PI3 K/AKT signal Reactive oxygen species Stem cells Tumor suppressor genes Tumorigenesis |
| title | Cytoglobin ameliorates the stemness of hepatocellular carcinoma via coupling oxidative‐nitrosative stress signals |
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