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DOI | 10.1038/ncomms14667 |
Blockade of leukemia inhibitory factor as a therapeutic approach to KRAS driven pancreatic cancer | |
Wang, Man-Tzu1,2,3; Fer, Nicole4; Galeas, Jacqueline3; Collisson, Eric A.3,5; Kim, Sung Eun3; Sharib, Jeremy6; McCormick, Frank3,4 | |
2019-07-11 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | KRAS mutations are present in over 90% of pancreatic ductal adenocarcinomas (PDAC), and drive their poor outcomes and failure to respond to targeted therapies. Here we show that Leukemia Inhibitory Factor (LIF) expression is induced specifically by oncogenic KRAS in PDAC and that LIF depletion by genetic means or by neutralizing antibodies prevents engraftment in pancreatic xenograft models. Moreover, LIF-neutralizing antibodies synergize with gemcitabine to eradicate established pancreatic tumors in a syngeneic, Kras(G12D)-driven, PDAC mouse model. The related cytokine IL-6 cannot substitute for LIF, suggesting that LIF mediates KRAS-driven malignancies through a non-STAT-signaling pathway. Unlike IL-6, LIF inhibits the activity of the Hippo-signaling pathway in PDACs. Depletion of YAP inhibits the function of LIF in human PDAC cells. Our data suggest a crucial role of LIF in KRAS-driven pancreatic cancer and that blockade of LIF by neutralizing antibodies represents an attractive approach to improving therapeutic outcomes. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000474824300002 |
WOS关键词 | CYTOKINE ; TUMORIGENICITY |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203232 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Pittsburgh, Tumor Microenvironm Ctr, UPMC Hillman Canc Ctr, Pittsburgh, PA 15213 USA; 2.Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA; 3.Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA; 4.Frederick Natl Lab Canc Res, NCI RAS Initiat, Canc Res Technol Program, Frederick, MD 21702 USA; 5.Univ Calif San Francisco, Dept Med Hematol & Oncol, San Francisco, CA 94143 USA; 6.Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA |
推荐引用方式 GB/T 7714 | Wang, Man-Tzu,Fer, Nicole,Galeas, Jacqueline,et al. Blockade of leukemia inhibitory factor as a therapeutic approach to KRAS driven pancreatic cancer[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Wang, Man-Tzu.,Fer, Nicole.,Galeas, Jacqueline.,Collisson, Eric A..,Kim, Sung Eun.,...&McCormick, Frank.(2019).Blockade of leukemia inhibitory factor as a therapeutic approach to KRAS driven pancreatic cancer.NATURE COMMUNICATIONS,10. |
MLA | Wang, Man-Tzu,et al."Blockade of leukemia inhibitory factor as a therapeutic approach to KRAS driven pancreatic cancer".NATURE COMMUNICATIONS 10(2019). |
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