Hepatocellular Carcinoma Repression by TNF alpha-Mediated Synergistic Lethal Effect of Mitosis Defect-Induced Senescence and Cell Death Sensitization
文献类型：期刊论文
| 作者 | Li, Dan4; Fu, Jing6; Du, Min7; Zhang, Haibin6; Li, Lu4; Cen, Jin4; Li, Weiyun4; Chen, Xiaotao4; Lin, Yunfei1; Conway, Edward M.2 |
| 刊名 | HEPATOLOGY
 |
| 出版日期 | 2016-10 |
| 卷号 | 64期号:4页码:1105-1120 |
| ISSN号 | 0270-9139 |
| DOI | 10.1002/hep.28637 |
| 文献子类 | Article |
| 英文摘要 | Hepatocellular carcinoma (HCC) is a cancer lacking effective therapies. Several measures have been proposed to treat HCCs, such as senescence induction, mitotic inhibition, and cell death promotion. However, data from other cancers suggest that single use of these approaches may not be effective. Here, by genetic targeting of Survivin, an inhibitor of apoptosis protein (IAP) that plays dual roles in mitosis and cell survival, we identified a tumor necrosis factor alpha (TNF alpha)-mediated synergistic lethal effect between senescence and apoptosis sensitization in malignant HCCs. Survivin deficiency results in mitosis defect-associated senescence in HCC cells, which triggers local inflammation and increased TNF alpha. Survivin inactivation also sensitizes HCC cells to TNF alpha-triggered cell death, which leads to marked HCC regression. Based on these findings, we designed a combination treatment using mitosis inhibitor and proapoptosis compounds. This treatment recapitulates the therapeutic effect of Survivin deletion and effectively eliminates HCCs, thus representing a potential strategy for HCC therapy. Conclusion: Survivin ablation dramatically suppresses human and mouse HCCs by triggering senescence-associated TNF alpha and sensitizing HCC cells to TNF alpha-induced cell death. Combined use of mitotic inhibitor and second mitochondrial-derived activator of caspases mimetic can induce senescence-associated TNF alpha and enhance TNF alpha-induced cell death and synergistically eliminate HCC. |
| WOS关键词 | PHASE-II TRIAL ; POLO-LIKE KINASES ; INHIBITOR BI 2536 ; LIVER-CANCER ; APOPTOSIS PROTEINS ; AURORA KINASES ; TUMOR-GROWTH ; SURVIVIN ; YM155 ; DRUG |
| 资助项目 | Ministry of Science and Technology (MOST) of China[2014CB910601] ; Ministry of Science and Technology (MOST) of China[2012CB945001] ; Ministry of Science and Technology (MOST) of China[2012ZX10002] ; National Science Foundation of China (NSFC)[31225016] ; National Science Foundation of China (NSFC)[31501111] ; National Science Foundation of China (NSFC)[81221061] ; National Science Foundation of China (NSFC)[81471948] ; Shanghai Science and Technology Committee[15JC1400200] ; Shanghai Science and Technology Committee[14XD1404200] ; Postdoctor Research Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences[2014KIP302] ; China Postdoctoral Science Foundation[2015M580361] |
| WOS研究方向 | Gastroenterology & Hepatology |
| 语种 | 英语 |
| WOS记录号 | WOS:000384552300012 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275882]  |
| 专题 | 药物安全性评价中心 |
| 通讯作者 | Ji, Yuan; Wang, Hong-Yang; Hui, Lijian |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, Shanghai, Peoples R China; 2.Univ British Columbia, Div Hematol Oncol, Dept Med, Ctr Blood Res, Vancouver, BC, Canada; 3.Hadassah Hebrew Univ, Med Ctr, Dept Immunol & Canc Res, Inst Med Res Israel Canada, Jerusalem, Israel; 4.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, State Key Lab Cell Biol, Room 915,New Biochem Bldg,320 Yueyang Rd, Shanghai 200031, Peoples R China; 5.Hadassah Hebrew Univ, Med Ctr, Dept Pathol, Jerusalem, Israel 6.Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, 225 Changhai Rd, Shanghai 200438, Peoples R China; 7.Fudan Univ, Zhongshan Hosp, Dept Pathol, 180 Fenglin Rd, Shanghai 200032, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Li, Dan,Fu, Jing,Du, Min,et al. Hepatocellular Carcinoma Repression by TNF alpha-Mediated Synergistic Lethal Effect of Mitosis Defect-Induced Senescence and Cell Death Sensitization[J]. HEPATOLOGY,2016,64(4):1105-1120. |
| APA | Li, Dan.,Fu, Jing.,Du, Min.,Zhang, Haibin.,Li, Lu.,...&Hui, Lijian.(2016).Hepatocellular Carcinoma Repression by TNF alpha-Mediated Synergistic Lethal Effect of Mitosis Defect-Induced Senescence and Cell Death Sensitization.HEPATOLOGY,64(4),1105-1120. |
| MLA | Li, Dan,et al."Hepatocellular Carcinoma Repression by TNF alpha-Mediated Synergistic Lethal Effect of Mitosis Defect-Induced Senescence and Cell Death Sensitization".HEPATOLOGY 64.4(2016):1105-1120. |
入库方式： OAI收割
来源：上海药物研究所
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