Arsenic trioxide (ATO) induced degradation of Cyclin D1 sensitized PD-1/PD-L1 checkpoint inhibitor in oral and esophageal squamous cell carcinoma
文献类型：期刊论文
| 作者 | Zhu, Guanxia2; Li, Xia3; Li, Jiong4; Zhou, Wei5; Chen, Zhongjian3; Fan, Yun3; Jiang, Youhua3; Zhao, Yue3; Sun, Guogui1; Mao, Weimin2 |
| 刊名 | JOURNAL OF CANCER
 |
| 出版日期 | 2020 |
| 卷号 | 11 |
| ISSN号 | 1837-9664 |
| 关键词 | esophageal squamous cell carcinoma oral squamous cell carcinoma arsenic trioxide cyclin D1 PD-L1 CDK4/6 |
| DOI | 10.7150/jca.47111 |
| 通讯作者 | Zhao, Yue(zhaoyue@zjcc.org.cn) ; Sun, Guogui(guogui_sun2013@163.com) ; Mao, Weimin(weimin.mao@zjcc.org.cn) |
| 英文摘要 | 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. |
| WOS关键词 | OPEN-LABEL ; CANCER ; THERAPY ; PROTEOLYSIS ; RESISTANCE ; APOPTOSIS ; ARREST ; GENES ; PD-L1 |
| 资助项目 | National Natural Science Foundation of China[81802472] ; Zhejiang Province Public Welfare Technology Application Research Project[LGJ18H310001] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| 出版者 | IVYSPRING INT PUBL |
| WOS记录号 | WOS:000575099000006 |
| 资助机构 | National Natural Science Foundation of China ; Zhejiang Province Public Welfare Technology Application Research Project |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/104350]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Zhao, Yue; Sun, Guogui; Mao, Weimin |
| 作者单位 | 1.North China Univ Sci & Technol, Affiliated Peoples Hosp, Sch Publ Hlth, Tangshan 063001, Peoples R China 2.Wenzhou Med Univ, Wenzhou 325035, Peoples R China 3.Chinese Acad Sci, Zhejiang Canc Hosp, Univ Chinese Acad Sci, Inst Canc & Basic Med,Canc Hosp, Hangzhou 310022, Peoples R China 4.Virginia Commonwealth Univ, Massey Canc Ctr, Philips Inst Oral Hlth Res, Dept Med Chem, Richmond, VA 23298 USA 5.Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Mol Oncol, Natl Canc Ctr, Natl Clin Res Ctr Canc,Canc Hosp, Beijing 100021, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhu, Guanxia,Li, Xia,Li, Jiong,et al. Arsenic trioxide (ATO) induced degradation of Cyclin D1 sensitized PD-1/PD-L1 checkpoint inhibitor in oral and esophageal squamous cell carcinoma[J]. JOURNAL OF CANCER,2020,11. |
| APA | Zhu, Guanxia.,Li, Xia.,Li, Jiong.,Zhou, Wei.,Chen, Zhongjian.,...&Mao, Weimin.(2020).Arsenic trioxide (ATO) induced degradation of Cyclin D1 sensitized PD-1/PD-L1 checkpoint inhibitor in oral and esophageal squamous cell carcinoma.JOURNAL OF CANCER,11. |
| MLA | Zhu, Guanxia,et al."Arsenic trioxide (ATO) induced degradation of Cyclin D1 sensitized PD-1/PD-L1 checkpoint inhibitor in oral and esophageal squamous cell carcinoma".JOURNAL OF CANCER 11(2020). |
入库方式： OAI收割
来源：合肥物质科学研究院
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