Upregulation of SIRT6 predicts poor prognosis and promotes metastasis of non-small cell lung cancer via the ERK1/2/MMP9 pathway
Sirtuin6 (SIRT6), a member of the sirtuins protein family, plays multiple complex roles in cancer. Here, we report that elevated SIRT6 expression was correlated with clinicopathological parameters such as T and N classification in non-small cell lung cancer (NSCLC) patient tumors. SIRT6 overexpressi...
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| Veröffentlicht in: | Oncotarget 2016-06, Vol.7 (26), p.40377-40386 |
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| creator | Bai, Lihong Lin, Gengpeng Sun, Longhua Liu, Yangli Huang, Xinyan Cao, Chuangjie Guo, Yubiao Xie, Canmao |
| description | Sirtuin6 (SIRT6), a member of the sirtuins protein family, plays multiple complex roles in cancer. Here, we report that elevated SIRT6 expression was correlated with clinicopathological parameters such as T and N classification in non-small cell lung cancer (NSCLC) patient tumors. SIRT6 overexpression in NSCLC cell lines increased extracellular signal-regulated kinase (p-ERK)1/2 phosphorylation, activated matrix metalloproteinase 9 (MMP9) and promoted tumor cell migration and invasion. Upon treatment with a specific mitogen-activated protein kinase (MEK) 1/2 inhibitor, these effects were abolished. Our results demonstrate SIRT6 upregulation in NSCLC for the first time and suggest a functional role for SIRT6 in promoting migration and invasion through ERK1/2/MMP9 signaling. SIRT6 may serve as a potential therapeutic target in NSCLC and its utility as a prognostic indicator warrants further study. |
| doi_str_mv | 10.18632/oncotarget.9750 |
| format | Article |
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Here, we report that elevated SIRT6 expression was correlated with clinicopathological parameters such as T and N classification in non-small cell lung cancer (NSCLC) patient tumors. SIRT6 overexpression in NSCLC cell lines increased extracellular signal-regulated kinase (p-ERK)1/2 phosphorylation, activated matrix metalloproteinase 9 (MMP9) and promoted tumor cell migration and invasion. Upon treatment with a specific mitogen-activated protein kinase (MEK) 1/2 inhibitor, these effects were abolished. Our results demonstrate SIRT6 upregulation in NSCLC for the first time and suggest a functional role for SIRT6 in promoting migration and invasion through ERK1/2/MMP9 signaling. SIRT6 may serve as a potential therapeutic target in NSCLC and its utility as a prognostic indicator warrants further study.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.9750</identifier><identifier>PMID: 27777384</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>A549 Cells ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Carcinoma, Non-Small-Cell Lung - metabolism ; Carcinoma, Non-Small-Cell Lung - pathology ; Cell Movement ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Male ; Matrix Metalloproteinase 9 - metabolism ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Phosphorylation ; Prognosis ; Research Paper ; Sirtuins - metabolism</subject><ispartof>Oncotarget, 2016-06, Vol.7 (26), p.40377-40386</ispartof><rights>Copyright: © 2016 Bai et al. 2016</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c490t-d29dfac1ee7f2a68d0b23fb1b350e087388bd21c11b68862dda1e694ceda91f23</citedby><cites>FETCH-LOGICAL-c490t-d29dfac1ee7f2a68d0b23fb1b350e087388bd21c11b68862dda1e694ceda91f23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5130014/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5130014/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27777384$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bai, Lihong</creatorcontrib><creatorcontrib>Lin, Gengpeng</creatorcontrib><creatorcontrib>Sun, Longhua</creatorcontrib><creatorcontrib>Liu, Yangli</creatorcontrib><creatorcontrib>Huang, Xinyan</creatorcontrib><creatorcontrib>Cao, Chuangjie</creatorcontrib><creatorcontrib>Guo, Yubiao</creatorcontrib><creatorcontrib>Xie, Canmao</creatorcontrib><title>Upregulation of SIRT6 predicts poor prognosis and promotes metastasis of non-small cell lung cancer via the ERK1/2/MMP9 pathway</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Sirtuin6 (SIRT6), a member of the sirtuins protein family, plays multiple complex roles in cancer. 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SIRT6 may serve as a potential therapeutic target in NSCLC and its utility as a prognostic indicator warrants further study.</description><subject>A549 Cells</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers, Tumor</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Cell Movement</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Silencing</subject><subject>Humans</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>Middle Aged</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Metastasis</subject><subject>Phosphorylation</subject><subject>Prognosis</subject><subject>Research Paper</subject><subject>Sirtuins - metabolism</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUctu1TAQjRAVrUr3rJCXbNLrRx72BglVBSpaUfWxtib2JDcosYPtFHXFr-NLS2lHI3sePmc8OkXxjtFjJhvBN94ZnyAMmI5VW9NXxQFTlSp5XYvXz-L94ijGHzRbXbWSqzfFPm-zCVkdFL9vl4DDOkEavSO-J9dnVzcNyUU7mhTJ4n3ImR-cj2Mk4Owum33CSGZMELPnegY678o4wzQRg_mYVjcQA85gIHcjkLRFcnr1jW345uLiUpEF0vYX3L8t9nqYIh493ofF7efTm5Ov5fn3L2cnn85LUymaSsuV7cEwxLbn0EhLOy76jnWipkhl3kV2ljPDWNdI2XBrgWGjKoMWFOu5OCw-PvAuazejNehSgEkvYZwh3GsPo37ZceNWD_5O10xQyqpM8OGRIPifK8ak5zHuNgWHfo2aSVE3bdW2u1n04akJPsaA_dMYRvVf6fR_6fROugx5__x7T4B_Qok_bGeaRg</recordid><startdate>20160628</startdate><enddate>20160628</enddate><creator>Bai, Lihong</creator><creator>Lin, Gengpeng</creator><creator>Sun, Longhua</creator><creator>Liu, Yangli</creator><creator>Huang, Xinyan</creator><creator>Cao, Chuangjie</creator><creator>Guo, Yubiao</creator><creator>Xie, Canmao</creator><general>Impact Journals LLC</general><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>5PM</scope></search><sort><creationdate>20160628</creationdate><title>Upregulation of SIRT6 predicts poor prognosis and promotes metastasis of non-small cell lung cancer via the ERK1/2/MMP9 pathway</title><author>Bai, Lihong ; Lin, Gengpeng ; Sun, Longhua ; Liu, Yangli ; Huang, Xinyan ; Cao, Chuangjie ; Guo, Yubiao ; Xie, Canmao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-d29dfac1ee7f2a68d0b23fb1b350e087388bd21c11b68862dda1e694ceda91f23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>A549 Cells</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers, Tumor</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Cell Movement</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Silencing</topic><topic>Humans</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>Matrix Metalloproteinase 9 - metabolism</topic><topic>Middle Aged</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Metastasis</topic><topic>Phosphorylation</topic><topic>Prognosis</topic><topic>Research Paper</topic><topic>Sirtuins - metabolism</topic><toplevel>online_resources</toplevel><creatorcontrib>Bai, Lihong</creatorcontrib><creatorcontrib>Lin, Gengpeng</creatorcontrib><creatorcontrib>Sun, Longhua</creatorcontrib><creatorcontrib>Liu, Yangli</creatorcontrib><creatorcontrib>Huang, Xinyan</creatorcontrib><creatorcontrib>Cao, Chuangjie</creatorcontrib><creatorcontrib>Guo, Yubiao</creatorcontrib><creatorcontrib>Xie, Canmao</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>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bai, Lihong</au><au>Lin, Gengpeng</au><au>Sun, Longhua</au><au>Liu, Yangli</au><au>Huang, Xinyan</au><au>Cao, Chuangjie</au><au>Guo, Yubiao</au><au>Xie, Canmao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Upregulation of SIRT6 predicts poor prognosis and promotes metastasis of non-small cell lung cancer via the ERK1/2/MMP9 pathway</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2016-06-28</date><risdate>2016</risdate><volume>7</volume><issue>26</issue><spage>40377</spage><epage>40386</epage><pages>40377-40386</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Sirtuin6 (SIRT6), a member of the sirtuins protein family, plays multiple complex roles in cancer. Here, we report that elevated SIRT6 expression was correlated with clinicopathological parameters such as T and N classification in non-small cell lung cancer (NSCLC) patient tumors. SIRT6 overexpression in NSCLC cell lines increased extracellular signal-regulated kinase (p-ERK)1/2 phosphorylation, activated matrix metalloproteinase 9 (MMP9) and promoted tumor cell migration and invasion. Upon treatment with a specific mitogen-activated protein kinase (MEK) 1/2 inhibitor, these effects were abolished. Our results demonstrate SIRT6 upregulation in NSCLC for the first time and suggest a functional role for SIRT6 in promoting migration and invasion through ERK1/2/MMP9 signaling. SIRT6 may serve as a potential therapeutic target in NSCLC and its utility as a prognostic indicator warrants further study.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>27777384</pmid><doi>10.18632/oncotarget.9750</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | A549 Cells Adult Aged Aged, 80 and over Biomarkers, Tumor Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - pathology Cell Movement Extracellular Signal-Regulated MAP Kinases - metabolism Female Gene Expression Regulation, Neoplastic Gene Silencing Humans Lung Neoplasms - metabolism Lung Neoplasms - pathology Male Matrix Metalloproteinase 9 - metabolism Middle Aged Neoplasm Invasiveness Neoplasm Metastasis Phosphorylation Prognosis Research Paper Sirtuins - metabolism |
| title | Upregulation of SIRT6 predicts poor prognosis and promotes metastasis of non-small cell lung cancer via the ERK1/2/MMP9 pathway |
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