The secretome engages STAT3 to favor a cytokine-rich microenvironment in mediating acquired resistance to FGFR inhibitors
文献类型：期刊论文
| 作者 | Wang, Xinyi1; Ai, Jing2 ; Liu, Hongyan1; Peng, Xia2; Chen, Hui1; Chen, Yi2; Su, Yi3; Shen, Aijun2; Huang, Xun2; Ding, Jian3
|
| 刊名 | Molecular cancer therapeutics
 |
| 出版日期 | 2018-12-06 |
| 卷号 | 145页码:817-842 |
| ISSN号 | 1538-8514 |
| 关键词 | 1,4-Diaryl-2-azetidinone Combretastatin A-4 Tubulin polymerization Antitumor |
| DOI | 10.1158/1535-7163.MCT-18-0179 |
| 文献子类 | Article |
| 英文摘要 | Acquired resistance severely hinders the application of small molecule inhibitors. Our understanding of acquired resistance related to fibroblast growth factor receptors (FGFRs) is limited. Here, to explore the underlying mechanism of acquired resistance in FGFR-aberrant cancer cells, we generated cells resistant to multiple FGFR inhibitors and investigated the potential mechanisms underlying acquired resistance. We discovered that reprogramming of the secretome is closely associated with acquired resistance to FGFR inhibitors. The secretome drives acquired resistance by activating the transcription factor STAT3 via its cognate receptors. Moreover, macrophages and fibroblasts could interact with cancer cells to enhance acquired resistance by promoting exaggerated and dynamic cytokine secretion, as well as STAT3 activation. We also found that Hsp90 and HDAC inhibitors could substantially and simultaneously suppress the proliferation of resistant cells, the secretion of multiple cytokines and the activation of STAT3. Our study offers translational insights concerning the poor efficacy observed in patients with macrophage- and fibroblast-rich lung cancers and breast tumors after treatment with FGFR inhibitors in clinical trials. |
| WOS关键词 | ASYMMETRIC ALLYLIC AMINATION ; BAYLIS-HILLMAN ADDUCTS ; ANTICANCER AGENTS ; POLYMERIZATION INHIBITOR ; DERIVATIVES ; CELLS ; MECHANISMS ; PHOSPHATE ; DISCOVERY ; MOLECULE |
| 资助项目 | National Natural Science Foundation of China[21472025] ; NSFC[21472208] ; NSFC[81625022] ; NSFC[81430084] ; NSFC[21232009] ; CAS[QYZDY-SSW-SLH012] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| WOS记录号 | WOS:000425198100062 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/266252]  |
| 专题 | 新药研究国家重点实验室 药理学第一研究室 |
| 通讯作者 | Ai, Jing |
| 作者单位 | 1.Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences; 2.Anti-tumor Pharmacology, Shanghai Institute of Material Medica; 3.Anti-tumor Pharmacology, Shanghai Institute of Materia Medica |
| 推荐引用方式 GB/T 7714 | Wang, Xinyi,Ai, Jing,Liu, Hongyan,et al. The secretome engages STAT3 to favor a cytokine-rich microenvironment in mediating acquired resistance to FGFR inhibitors[J]. Molecular cancer therapeutics,2018,145:817-842. |
| APA | Wang, Xinyi.,Ai, Jing.,Liu, Hongyan.,Peng, Xia.,Chen, Hui.,...&Geng, Meiyu.(2018).The secretome engages STAT3 to favor a cytokine-rich microenvironment in mediating acquired resistance to FGFR inhibitors.Molecular cancer therapeutics,145,817-842. |
| MLA | Wang, Xinyi,et al."The secretome engages STAT3 to favor a cytokine-rich microenvironment in mediating acquired resistance to FGFR inhibitors".Molecular cancer therapeutics 145(2018):817-842. |
入库方式： OAI收割
来源：上海药物研究所
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