Arsenic trioxide (ATO) induced degradation of Cyclin D1 sensitized PD-1/PD-L1 checkpoint inhibitor in oral and esophageal squamous cell carcinoma
Arsenic trioxide (ATO) is widely studied for its antitumor efficacy and several recent studies suggested the immune modulatory effects of ATO in animal models. In this study we found ATO treatment induced increased ROS production and DNA damage in esophageal squamous cell carcinoma (ESCC) cells, led...
Gespeichert in:
| Veröffentlicht in: | Journal of Cancer 2020-01, Vol.11 (22), p.6516-6529 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 6529 |
|---|---|
| container_issue | 22 |
| container_start_page | 6516 |
| container_title | Journal of Cancer |
| container_volume | 11 |
| creator | Zhu, Guanxia Li, Xia Li, Jiong Zhou, Wei Chen, Zhongjian Fan, Yun Jiang, Youhua Zhao, Yue Sun, Guogui Mao, Weimin |
| description | Arsenic trioxide (ATO) is widely studied for its antitumor efficacy and several recent studies suggested the immune modulatory effects of ATO in animal models. In this study we found ATO treatment induced increased ROS production and DNA damage in esophageal squamous cell carcinoma (ESCC) cells, led to DNA damage mediated degradation of Cyclin D1 and upregulation of PD-L1 in these cancer cells. Mechanistically, we found ATO induced a transient upregulation and nuclear translocation of Cyclin D1 by sumoylation. Followed with increased ubiquitination and degradation of Cyclin D1 through T286 phosphorylation, and at least partly mediated by Stat1 Y701 phosphorylation. We observed inversed correlations between Cyclin D1 and PD-L1 expression levels in human ESCC tissues. With 4NQO induced PD-L1 humanized mouse oral and esophageal squamous carcinoma model, we found combinatory administration of ATO and check point inhibitor resulted in a significant reduction of tumor volumes. Inversed correlation between Cyclin D1 with PD-L1 was also observed in the 4NQO induced mouse ESCC and OSCC model. Together, these data suggested ATO induced degradation of Cyclin D1 and functional suppression of CDK4/6 pathway sensitized OSCC and ESCC to checkpoint inhibitor treatment. |
| doi_str_mv | 10.7150/jca.47111 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7545676</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2450667359</sourcerecordid><originalsourceid>FETCH-LOGICAL-c380t-fcdda44512d7d7aa1267909c9e09f66feb0cdc634fcf7b7bd47be9b5504450983</originalsourceid><addsrcrecordid>eNpdUctOJCEUJWaMGnXhH5DMRhelUFDQbCbptPMw6UQXuibUheqmpwpaqDLj_MX88eAjRmUB94Zzzz0nB6ETSs4lbcjFBsw5l5TSHXRAZ0xWSgj-5V29j45z3pBymKolZ3tonzHChZLsAP2bp-yCBzwmH_946_Dp_Pb6DPtgJ3AWW7dKxprRx4BjhxeP0PuALykuU9mP_m_B3FxW9KJcS4ph7eD3NvowFoa1b_0YU6lwTKbHJljsctyuzcqVNt9PZohTxuD6HoNJ4EMczBHa7Uyf3fHre4jufny_Xfyqltc_rxbzZQVsRsaqA2sN5w2trbTSGFoLqYgC5YjqhOhcS8CCYLyDTraytVy2TrVNQ8oQUTN2iL698G6ndnAWXBiLSL1NfjDpUUfj9cef4Nd6FR-0bHgjpCgEp68EKd5PLo968PnJiwmu2NJ12SOEZI0q0K-foJs4pVDs6bopWuqaPBOevaAgxZyT697EUKKfstYla_2cNfsP6UScAg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2598322076</pqid></control><display><type>article</type><title>Arsenic trioxide (ATO) induced degradation of Cyclin D1 sensitized PD-1/PD-L1 checkpoint inhibitor in oral and esophageal squamous cell carcinoma</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central Open Access</source><source>PubMed Central</source><creator>Zhu, Guanxia ; Li, Xia ; Li, Jiong ; Zhou, Wei ; Chen, Zhongjian ; Fan, Yun ; Jiang, Youhua ; Zhao, Yue ; Sun, Guogui ; Mao, Weimin</creator><creatorcontrib>Zhu, Guanxia ; Li, Xia ; Li, Jiong ; Zhou, Wei ; Chen, Zhongjian ; Fan, Yun ; Jiang, Youhua ; Zhao, Yue ; Sun, Guogui ; Mao, Weimin</creatorcontrib><description>Arsenic trioxide (ATO) is widely studied for its antitumor efficacy and several recent studies suggested the immune modulatory effects of ATO in animal models. In this study we found ATO treatment induced increased ROS production and DNA damage in esophageal squamous cell carcinoma (ESCC) cells, led to DNA damage mediated degradation of Cyclin D1 and upregulation of PD-L1 in these cancer cells. Mechanistically, we found ATO induced a transient upregulation and nuclear translocation of Cyclin D1 by sumoylation. Followed with increased ubiquitination and degradation of Cyclin D1 through T286 phosphorylation, and at least partly mediated by Stat1 Y701 phosphorylation. We observed inversed correlations between Cyclin D1 and PD-L1 expression levels in human ESCC tissues. With 4NQO induced PD-L1 humanized mouse oral and esophageal squamous carcinoma model, we found combinatory administration of ATO and check point inhibitor resulted in a significant reduction of tumor volumes. Inversed correlation between Cyclin D1 with PD-L1 was also observed in the 4NQO induced mouse ESCC and OSCC model. Together, these data suggested ATO induced degradation of Cyclin D1 and functional suppression of CDK4/6 pathway sensitized OSCC and ESCC to checkpoint inhibitor treatment.</description><identifier>ISSN: 1837-9664</identifier><identifier>EISSN: 1837-9664</identifier><identifier>DOI: 10.7150/jca.47111</identifier><identifier>PMID: 33046973</identifier><language>eng</language><publisher>Wyoming: Ivyspring International Publisher Pty Ltd</publisher><subject>Arsenic ; Cancer therapies ; Cell cycle ; Cytotoxicity ; DNA damage ; Esophageal cancer ; FDA approval ; Leukemia ; Liver cancer ; Lymphocytes ; Oral cancer ; Proteins ; Research Paper ; Squamous cell carcinoma</subject><ispartof>Journal of Cancer, 2020-01, Vol.11 (22), p.6516-6529</ispartof><rights>2020. This work is published 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>The author(s) 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c380t-fcdda44512d7d7aa1267909c9e09f66feb0cdc634fcf7b7bd47be9b5504450983</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545676/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545676/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,886,27926,27927,53793,53795</link.rule.ids></links><search><creatorcontrib>Zhu, Guanxia</creatorcontrib><creatorcontrib>Li, Xia</creatorcontrib><creatorcontrib>Li, Jiong</creatorcontrib><creatorcontrib>Zhou, Wei</creatorcontrib><creatorcontrib>Chen, Zhongjian</creatorcontrib><creatorcontrib>Fan, Yun</creatorcontrib><creatorcontrib>Jiang, Youhua</creatorcontrib><creatorcontrib>Zhao, Yue</creatorcontrib><creatorcontrib>Sun, Guogui</creatorcontrib><creatorcontrib>Mao, Weimin</creatorcontrib><title>Arsenic trioxide (ATO) induced degradation of Cyclin D1 sensitized PD-1/PD-L1 checkpoint inhibitor in oral and esophageal squamous cell carcinoma</title><title>Journal of Cancer</title><description>Arsenic trioxide (ATO) is widely studied for its antitumor efficacy and several recent studies suggested the immune modulatory effects of ATO in animal models. In this study we found ATO treatment induced increased ROS production and DNA damage in esophageal squamous cell carcinoma (ESCC) cells, led to DNA damage mediated degradation of Cyclin D1 and upregulation of PD-L1 in these cancer cells. Mechanistically, we found ATO induced a transient upregulation and nuclear translocation of Cyclin D1 by sumoylation. Followed with increased ubiquitination and degradation of Cyclin D1 through T286 phosphorylation, and at least partly mediated by Stat1 Y701 phosphorylation. We observed inversed correlations between Cyclin D1 and PD-L1 expression levels in human ESCC tissues. With 4NQO induced PD-L1 humanized mouse oral and esophageal squamous carcinoma model, we found combinatory administration of ATO and check point inhibitor resulted in a significant reduction of tumor volumes. Inversed correlation between Cyclin D1 with PD-L1 was also observed in the 4NQO induced mouse ESCC and OSCC model. Together, these data suggested ATO induced degradation of Cyclin D1 and functional suppression of CDK4/6 pathway sensitized OSCC and ESCC to checkpoint inhibitor treatment.</description><subject>Arsenic</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Cytotoxicity</subject><subject>DNA damage</subject><subject>Esophageal cancer</subject><subject>FDA approval</subject><subject>Leukemia</subject><subject>Liver cancer</subject><subject>Lymphocytes</subject><subject>Oral cancer</subject><subject>Proteins</subject><subject>Research Paper</subject><subject>Squamous cell carcinoma</subject><issn>1837-9664</issn><issn>1837-9664</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNpdUctOJCEUJWaMGnXhH5DMRhelUFDQbCbptPMw6UQXuibUheqmpwpaqDLj_MX88eAjRmUB94Zzzz0nB6ETSs4lbcjFBsw5l5TSHXRAZ0xWSgj-5V29j45z3pBymKolZ3tonzHChZLsAP2bp-yCBzwmH_946_Dp_Pb6DPtgJ3AWW7dKxprRx4BjhxeP0PuALykuU9mP_m_B3FxW9KJcS4ph7eD3NvowFoa1b_0YU6lwTKbHJljsctyuzcqVNt9PZohTxuD6HoNJ4EMczBHa7Uyf3fHre4jufny_Xfyqltc_rxbzZQVsRsaqA2sN5w2trbTSGFoLqYgC5YjqhOhcS8CCYLyDTraytVy2TrVNQ8oQUTN2iL698G6ndnAWXBiLSL1NfjDpUUfj9cef4Nd6FR-0bHgjpCgEp68EKd5PLo968PnJiwmu2NJ12SOEZI0q0K-foJs4pVDs6bopWuqaPBOevaAgxZyT697EUKKfstYla_2cNfsP6UScAg</recordid><startdate>20200101</startdate><enddate>20200101</enddate><creator>Zhu, Guanxia</creator><creator>Li, Xia</creator><creator>Li, Jiong</creator><creator>Zhou, Wei</creator><creator>Chen, Zhongjian</creator><creator>Fan, Yun</creator><creator>Jiang, Youhua</creator><creator>Zhao, Yue</creator><creator>Sun, Guogui</creator><creator>Mao, Weimin</creator><general>Ivyspring International Publisher Pty Ltd</general><general>Ivyspring International Publisher</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</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>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200101</creationdate><title>Arsenic trioxide (ATO) induced degradation of Cyclin D1 sensitized PD-1/PD-L1 checkpoint inhibitor in oral and esophageal squamous cell carcinoma</title><author>Zhu, Guanxia ; Li, Xia ; Li, Jiong ; Zhou, Wei ; Chen, Zhongjian ; Fan, Yun ; Jiang, Youhua ; Zhao, Yue ; Sun, Guogui ; Mao, Weimin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c380t-fcdda44512d7d7aa1267909c9e09f66feb0cdc634fcf7b7bd47be9b5504450983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Arsenic</topic><topic>Cancer therapies</topic><topic>Cell cycle</topic><topic>Cytotoxicity</topic><topic>DNA damage</topic><topic>Esophageal cancer</topic><topic>FDA approval</topic><topic>Leukemia</topic><topic>Liver cancer</topic><topic>Lymphocytes</topic><topic>Oral cancer</topic><topic>Proteins</topic><topic>Research Paper</topic><topic>Squamous cell carcinoma</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhu, Guanxia</creatorcontrib><creatorcontrib>Li, Xia</creatorcontrib><creatorcontrib>Li, Jiong</creatorcontrib><creatorcontrib>Zhou, Wei</creatorcontrib><creatorcontrib>Chen, Zhongjian</creatorcontrib><creatorcontrib>Fan, Yun</creatorcontrib><creatorcontrib>Jiang, Youhua</creatorcontrib><creatorcontrib>Zhao, Yue</creatorcontrib><creatorcontrib>Sun, Guogui</creatorcontrib><creatorcontrib>Mao, Weimin</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</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>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 Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</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 China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of Cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhu, Guanxia</au><au>Li, Xia</au><au>Li, Jiong</au><au>Zhou, Wei</au><au>Chen, Zhongjian</au><au>Fan, Yun</au><au>Jiang, Youhua</au><au>Zhao, Yue</au><au>Sun, Guogui</au><au>Mao, Weimin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Arsenic trioxide (ATO) induced degradation of Cyclin D1 sensitized PD-1/PD-L1 checkpoint inhibitor in oral and esophageal squamous cell carcinoma</atitle><jtitle>Journal of Cancer</jtitle><date>2020-01-01</date><risdate>2020</risdate><volume>11</volume><issue>22</issue><spage>6516</spage><epage>6529</epage><pages>6516-6529</pages><issn>1837-9664</issn><eissn>1837-9664</eissn><abstract>Arsenic trioxide (ATO) is widely studied for its antitumor efficacy and several recent studies suggested the immune modulatory effects of ATO in animal models. In this study we found ATO treatment induced increased ROS production and DNA damage in esophageal squamous cell carcinoma (ESCC) cells, led to DNA damage mediated degradation of Cyclin D1 and upregulation of PD-L1 in these cancer cells. Mechanistically, we found ATO induced a transient upregulation and nuclear translocation of Cyclin D1 by sumoylation. Followed with increased ubiquitination and degradation of Cyclin D1 through T286 phosphorylation, and at least partly mediated by Stat1 Y701 phosphorylation. We observed inversed correlations between Cyclin D1 and PD-L1 expression levels in human ESCC tissues. With 4NQO induced PD-L1 humanized mouse oral and esophageal squamous carcinoma model, we found combinatory administration of ATO and check point inhibitor resulted in a significant reduction of tumor volumes. Inversed correlation between Cyclin D1 with PD-L1 was also observed in the 4NQO induced mouse ESCC and OSCC model. Together, these data suggested ATO induced degradation of Cyclin D1 and functional suppression of CDK4/6 pathway sensitized OSCC and ESCC to checkpoint inhibitor treatment.</abstract><cop>Wyoming</cop><pub>Ivyspring International Publisher Pty Ltd</pub><pmid>33046973</pmid><doi>10.7150/jca.47111</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1837-9664 |
| ispartof | Journal of Cancer, 2020-01, Vol.11 (22), p.6516-6529 |
| issn | 1837-9664 1837-9664 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7545676 |
| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; PubMed Central |
| subjects | Arsenic Cancer therapies Cell cycle Cytotoxicity DNA damage Esophageal cancer FDA approval Leukemia Liver cancer Lymphocytes Oral cancer Proteins Research Paper Squamous cell carcinoma |
| title | Arsenic trioxide (ATO) induced degradation of Cyclin D1 sensitized PD-1/PD-L1 checkpoint inhibitor in oral and esophageal squamous cell carcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T09%3A04%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Arsenic%20trioxide%20(ATO)%20induced%20degradation%20of%20Cyclin%20D1%20sensitized%20PD-1/PD-L1%20checkpoint%20inhibitor%20in%20oral%20and%20esophageal%20squamous%20cell%20carcinoma&rft.jtitle=Journal%20of%20Cancer&rft.au=Zhu,%20Guanxia&rft.date=2020-01-01&rft.volume=11&rft.issue=22&rft.spage=6516&rft.epage=6529&rft.pages=6516-6529&rft.issn=1837-9664&rft.eissn=1837-9664&rft_id=info:doi/10.7150/jca.47111&rft_dat=%3Cproquest_pubme%3E2450667359%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2598322076&rft_id=info:pmid/33046973&rfr_iscdi=true |