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Membrane-bound TNF mediates microtubule-targeting chemotherapeutics-induced cancer cytolysis via juxtacrine inter-cancer-cell death signaling | |
2020-05 | |
发表期刊 | CELL DEATH AND DIFFERENTIATION (IF:13.7[JCR-2023],13.7[5-Year]) |
ISSN | 1350-9047 |
EISSN | 1476-5403 |
卷号 | 27期号:5页码:1569-1587 |
发表状态 | 已发表 |
DOI | 10.1038/s41418-019-0441-3 |
摘要 | Microtubule-targeting agents (MTAs) are a class of most widely used chemotherapeutics and their mechanism of action has long been assumed to be mitotic arrest of rapidly dividing tumor cells. In contrast to such notion, here we show-in many cancer cell types-MTAs function by triggering membrane TNF (memTNF)-mediated cancer-cell-to-cancer-cell killing, which differs greatly from other non-MTA cell-cycle-arresting agents. The killing is through programmed cell death (PCD), either in way of necroptosis when RIP3 kinase is expressed, or of apoptosis in its absence. Mechanistically, MTAs induce memTNF transcription via the JNK-cJun signaling pathway. With respect to chemotherapy regimens, our results establish that memTNF-mediated killing is significantly augmented by IAP antagonists (Smac mimetics) in a broad spectrum of cancer types, and with their effects most prominently manifested in patient-derived xenograft (PDX) models in which cell-cell contacts are highly reminiscent of human tumors. Therefore, our finding indicates that memTNF can serve as a marker for patient responsiveness, and Smac mimetics will be effective adjuvants for MTA chemotherapeutics. The present study reframes our fundamental biochemical understanding of how MTAs take advantage of the natural tight contact of tumor cells and utilize memTNF-mediated death signaling to induce the entire tumor regression. |
URL | 查看原文 |
收录类别 | SCI ; SCIE |
语种 | 英语 |
资助项目 | National Natural Science Foundation of China (National Science Foundation of China)[31471302][81530075] |
WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
WOS类目 | Biochemistry & Molecular Biology ; Cell Biology |
WOS记录号 | WOS:000528065200010 |
出版者 | NATURE PUBLISHING GROUP |
WOS关键词 | TUMOR-NECROSIS-FACTOR ; MIXED LINEAGE KINASE ; DOMAIN-LIKE PROTEIN ; FACTOR-ALPHA PROMOTER ; PROGRAMMED NECROSIS ; RECOMBINANT HUMAN ; L929 CELLS ; APOPTOSIS ; ACTIVATION ; EXPRESSION |
原始文献类型 | Article |
引用统计 | 正在获取...
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文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/120855 |
专题 | 生命科学与技术学院_PI研究组_王华翌组 生命科学与技术学院_博士生 |
通讯作者 | Liu, Suling; Sun, Liming |
作者单位 | 1.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Cell Biol,CAS Ctr Excellence Mol Ce, 320 Yueyang Rd, Shanghai 200031, Peoples R China 2.Fudan Univ, Shanghai Canc Ctr, Shanghai 200032, Peoples R China 3.Fudan Univ, Inst Biomed Sci, Shanghai Med Coll,Canc Inst, Key Lab Breast Canc Shanghai,Innovat Ctr Cell Sig, Shanghai 200032, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Nutr & Hlth,CAS Key Lab Computat Bi, CAS MPG Partner Inst Computat Biol,Collaborat Inn, Shanghai 200031, Peoples R China 5.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China |
推荐引用方式 GB/T 7714 | Zhang, Jing,Yang, Yu,Zhou, Shenao,et al. Membrane-bound TNF mediates microtubule-targeting chemotherapeutics-induced cancer cytolysis via juxtacrine inter-cancer-cell death signaling[J]. CELL DEATH AND DIFFERENTIATION,2020,27(5):1569-1587. |
APA | Zhang, Jing.,Yang, Yu.,Zhou, Shenao.,He, Xueyan.,Cao, Xuan.,...&Sun, Liming.(2020).Membrane-bound TNF mediates microtubule-targeting chemotherapeutics-induced cancer cytolysis via juxtacrine inter-cancer-cell death signaling.CELL DEATH AND DIFFERENTIATION,27(5),1569-1587. |
MLA | Zhang, Jing,et al."Membrane-bound TNF mediates microtubule-targeting chemotherapeutics-induced cancer cytolysis via juxtacrine inter-cancer-cell death signaling".CELL DEATH AND DIFFERENTIATION 27.5(2020):1569-1587. |
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