Overexpression of Lon contributes to survival and aggressive phenotype of cancer cells through mitochondrial complex I-mediated generation of reactive oxygen species
Lon protease is a multifunction protein and operates in protein quality control and stress response pathways in mitochondria. Human Lon is upregulated under oxidative and hypoxic stresses that represent the stress phenotypes of cancer. However, little literature undertakes comprehensive and detailed...
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| Veröffentlicht in: | Cell death & disease 2013-06, Vol.4 (6), p.e681-e681 |
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| creator | Cheng, C-W Kuo, C-Y Fan, C-C Fang, W-C Jiang, S S Lo, Y-K Wang, T-Y Kao, M-C Lee, A Y-L |
| description | Lon protease is a multifunction protein and operates in protein quality control and stress response pathways in mitochondria. Human Lon is upregulated under oxidative and hypoxic stresses that represent the stress phenotypes of cancer. However, little literature undertakes comprehensive and detailed investigations on the tumorigenic role of Lon. Overexpression of Lon promotes cell proliferation, apoptotic resistance to stresses, and transformation. Furthermore, Lon overexpression induces the production of mitochondrial reactive oxygen species (ROS) that result from Lon-mediated upregulation of NDUFS8, a mitochondrial Fe-S protein in complex I of electron transport chain. Increased level of mitochondrial ROS promotes cell proliferation, cell survival, cell migration, and epithelial–mesenchymal transition through mitogen-activated protein kinase (MAPK) and Ras-ERK activation. Overall, the present report for the first time demonstrates the role of Lon overexpression in tumorigenesis. Lon overexpression gives an apoptotic resistance to stresses and induces mitochondrial ROS production through Complex I as signaling molecules to activate Ras and MAPK signaling, giving the survival advantages and adaptation to cancer cells. Finally,
in silico
and immunohistochemistry analysis showed that Lon is overexpressed specifically in various types of cancer tissue including oral cancer. |
| doi_str_mv | 10.1038/cddis.2013.204 |
| format | Article |
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in silico
and immunohistochemistry analysis showed that Lon is overexpressed specifically in various types of cancer tissue including oral cancer.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/cddis.2013.204</identifier><identifier>PMID: 23788038</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/2327 ; 631/80/82/23 ; 692/420 ; Antibodies ; Biochemistry ; Biomedical and Life Sciences ; Carcinogenesis - metabolism ; Carcinoma, Squamous Cell - enzymology ; Cell Biology ; Cell Culture ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cell Survival ; Enzyme Stability ; Epithelial-Mesenchymal Transition ; Gene Expression ; HEK293 Cells ; Humans ; Immunology ; Life Sciences ; MAP Kinase Signaling System ; Mitochondria - enzymology ; Mouth Neoplasms - enzymology ; NADH Dehydrogenase - metabolism ; Original ; original-article ; Phenotype ; Protease La - genetics ; Protease La - metabolism ; Superoxides - metabolism ; Up-Regulation</subject><ispartof>Cell death & disease, 2013-06, Vol.4 (6), p.e681-e681</ispartof><rights>The Author(s) 2013</rights><rights>Copyright Nature Publishing Group Jun 2013</rights><rights>Copyright © 2013 Macmillan Publishers Limited 2013 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c557t-996b77478d7993a007b7a594deb38ca0e8c7ff03ef4268836855be8fba4313eb3</citedby><cites>FETCH-LOGICAL-c557t-996b77478d7993a007b7a594deb38ca0e8c7ff03ef4268836855be8fba4313eb3</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/PMC3702277/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3702277/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23788038$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cheng, C-W</creatorcontrib><creatorcontrib>Kuo, C-Y</creatorcontrib><creatorcontrib>Fan, C-C</creatorcontrib><creatorcontrib>Fang, W-C</creatorcontrib><creatorcontrib>Jiang, S S</creatorcontrib><creatorcontrib>Lo, Y-K</creatorcontrib><creatorcontrib>Wang, T-Y</creatorcontrib><creatorcontrib>Kao, M-C</creatorcontrib><creatorcontrib>Lee, A Y-L</creatorcontrib><title>Overexpression of Lon contributes to survival and aggressive phenotype of cancer cells through mitochondrial complex I-mediated generation of reactive oxygen species</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>Lon protease is a multifunction protein and operates in protein quality control and stress response pathways in mitochondria. Human Lon is upregulated under oxidative and hypoxic stresses that represent the stress phenotypes of cancer. However, little literature undertakes comprehensive and detailed investigations on the tumorigenic role of Lon. Overexpression of Lon promotes cell proliferation, apoptotic resistance to stresses, and transformation. Furthermore, Lon overexpression induces the production of mitochondrial reactive oxygen species (ROS) that result from Lon-mediated upregulation of NDUFS8, a mitochondrial Fe-S protein in complex I of electron transport chain. Increased level of mitochondrial ROS promotes cell proliferation, cell survival, cell migration, and epithelial–mesenchymal transition through mitogen-activated protein kinase (MAPK) and Ras-ERK activation. Overall, the present report for the first time demonstrates the role of Lon overexpression in tumorigenesis. Lon overexpression gives an apoptotic resistance to stresses and induces mitochondrial ROS production through Complex I as signaling molecules to activate Ras and MAPK signaling, giving the survival advantages and adaptation to cancer cells. Finally,
in silico
and immunohistochemistry analysis showed that Lon is overexpressed specifically in various types of cancer tissue including oral cancer.</description><subject>631/67/2327</subject><subject>631/80/82/23</subject><subject>692/420</subject><subject>Antibodies</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Carcinogenesis - metabolism</subject><subject>Carcinoma, Squamous Cell - enzymology</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Cell Survival</subject><subject>Enzyme Stability</subject><subject>Epithelial-Mesenchymal Transition</subject><subject>Gene Expression</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Immunology</subject><subject>Life Sciences</subject><subject>MAP Kinase Signaling System</subject><subject>Mitochondria - enzymology</subject><subject>Mouth Neoplasms - enzymology</subject><subject>NADH Dehydrogenase - metabolism</subject><subject>Original</subject><subject>original-article</subject><subject>Phenotype</subject><subject>Protease La - genetics</subject><subject>Protease La - metabolism</subject><subject>Superoxides - metabolism</subject><subject>Up-Regulation</subject><issn>2041-4889</issn><issn>2041-4889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkk1r3DAQhk1paUKaa49F0Esv3siWbcmXQgn9CCzk0p6FLI9tBVtyJdns_qD-z85mN2FTqsNIMM-886FJkvcZ3WSUiRvdtiZscpoxNMWr5BJtlhZC1K_P3hfJdQgPFA9jNC-rt8lFzrgQqHCZ_LlfwcNu9hCCcZa4jmzx0s5Gb5olQiDRkbD41axqJMq2RPX9I70CmQewLu5nOMRpZTV4omEcMWjwbukHMpno9OBs6w2GazfNI-zIXTpBa1SElvRgwat4yu1B6XhQdrs9ekiYQRsI75I3nRoDXJ_uq-TXt68_b3-k2_vvd7dftqkuSx7Tuq4azgsuWl7XTFHKG67KumihYUIrCkLzrqMMuiKvhGCVKMsGRNeogmUMoavk81F3XhqsUANOQY1y9mZSfi-dMvKlx5pB9m6VjNM85xwFPp0EvPu9QIhyMuEwEWXBLUFmvKZ1xXhVIvrxH_TBLd5ie0iJKqclryqkNkdKexeCh-65mIzKwxLIxyWQhyVAU2DAh_MWnvGnL0fg5ggEdNke_Fne_0v-BWT2wwQ</recordid><startdate>20130601</startdate><enddate>20130601</enddate><creator>Cheng, C-W</creator><creator>Kuo, C-Y</creator><creator>Fan, C-C</creator><creator>Fang, W-C</creator><creator>Jiang, S S</creator><creator>Lo, Y-K</creator><creator>Wang, T-Y</creator><creator>Kao, M-C</creator><creator>Lee, A Y-L</creator><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><general>Nature Publishing Group</general><scope>C6C</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7TO</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20130601</creationdate><title>Overexpression of Lon contributes to survival and aggressive phenotype of cancer cells through mitochondrial complex I-mediated generation of reactive oxygen species</title><author>Cheng, C-W ; Kuo, C-Y ; Fan, C-C ; Fang, W-C ; Jiang, S S ; Lo, Y-K ; Wang, T-Y ; Kao, M-C ; Lee, A Y-L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c557t-996b77478d7993a007b7a594deb38ca0e8c7ff03ef4268836855be8fba4313eb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>631/67/2327</topic><topic>631/80/82/23</topic><topic>692/420</topic><topic>Antibodies</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Carcinogenesis - metabolism</topic><topic>Carcinoma, Squamous Cell - enzymology</topic><topic>Cell Biology</topic><topic>Cell Culture</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Cell Survival</topic><topic>Enzyme Stability</topic><topic>Epithelial-Mesenchymal Transition</topic><topic>Gene Expression</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Immunology</topic><topic>Life Sciences</topic><topic>MAP Kinase Signaling System</topic><topic>Mitochondria - enzymology</topic><topic>Mouth Neoplasms - enzymology</topic><topic>NADH Dehydrogenase - metabolism</topic><topic>Original</topic><topic>original-article</topic><topic>Phenotype</topic><topic>Protease La - genetics</topic><topic>Protease La - metabolism</topic><topic>Superoxides - metabolism</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cheng, C-W</creatorcontrib><creatorcontrib>Kuo, C-Y</creatorcontrib><creatorcontrib>Fan, C-C</creatorcontrib><creatorcontrib>Fang, W-C</creatorcontrib><creatorcontrib>Jiang, S S</creatorcontrib><creatorcontrib>Lo, Y-K</creatorcontrib><creatorcontrib>Wang, T-Y</creatorcontrib><creatorcontrib>Kao, M-C</creatorcontrib><creatorcontrib>Lee, A Y-L</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><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>Biology Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</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>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Science Database</collection><collection>Biological Science Database</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>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death & disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cheng, C-W</au><au>Kuo, C-Y</au><au>Fan, C-C</au><au>Fang, W-C</au><au>Jiang, S S</au><au>Lo, Y-K</au><au>Wang, T-Y</au><au>Kao, M-C</au><au>Lee, A Y-L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overexpression of Lon contributes to survival and aggressive phenotype of cancer cells through mitochondrial complex I-mediated generation of reactive oxygen species</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2013-06-01</date><risdate>2013</risdate><volume>4</volume><issue>6</issue><spage>e681</spage><epage>e681</epage><pages>e681-e681</pages><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>Lon protease is a multifunction protein and operates in protein quality control and stress response pathways in mitochondria. Human Lon is upregulated under oxidative and hypoxic stresses that represent the stress phenotypes of cancer. However, little literature undertakes comprehensive and detailed investigations on the tumorigenic role of Lon. Overexpression of Lon promotes cell proliferation, apoptotic resistance to stresses, and transformation. Furthermore, Lon overexpression induces the production of mitochondrial reactive oxygen species (ROS) that result from Lon-mediated upregulation of NDUFS8, a mitochondrial Fe-S protein in complex I of electron transport chain. Increased level of mitochondrial ROS promotes cell proliferation, cell survival, cell migration, and epithelial–mesenchymal transition through mitogen-activated protein kinase (MAPK) and Ras-ERK activation. Overall, the present report for the first time demonstrates the role of Lon overexpression in tumorigenesis. Lon overexpression gives an apoptotic resistance to stresses and induces mitochondrial ROS production through Complex I as signaling molecules to activate Ras and MAPK signaling, giving the survival advantages and adaptation to cancer cells. Finally,
in silico
and immunohistochemistry analysis showed that Lon is overexpressed specifically in various types of cancer tissue including oral cancer.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23788038</pmid><doi>10.1038/cddis.2013.204</doi><oa>free_for_read</oa></addata></record> |
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| subjects | 631/67/2327 631/80/82/23 692/420 Antibodies Biochemistry Biomedical and Life Sciences Carcinogenesis - metabolism Carcinoma, Squamous Cell - enzymology Cell Biology Cell Culture Cell Line, Tumor Cell Movement Cell Proliferation Cell Survival Enzyme Stability Epithelial-Mesenchymal Transition Gene Expression HEK293 Cells Humans Immunology Life Sciences MAP Kinase Signaling System Mitochondria - enzymology Mouth Neoplasms - enzymology NADH Dehydrogenase - metabolism Original original-article Phenotype Protease La - genetics Protease La - metabolism Superoxides - metabolism Up-Regulation |
| title | Overexpression of Lon contributes to survival and aggressive phenotype of cancer cells through mitochondrial complex I-mediated generation of reactive oxygen species |
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