FAK inhibitors induce cell multinucleation and dramatically increase pro-tumoral cytokine expression in RAW 264.7 macrophages
文献类型：期刊论文
| 作者 | He, X; Chen, X; Li, BG; Ji, JX; Chen, S; Chen, S (reprint author), Chinese Acad Sci, Chengdu Inst Biol, Chengdu 610041, Sichuan, Peoples R China. |
| 刊名 | FEBS LETTERS
 |
| 出版日期 | 2017 |
| 卷号 | 591期号:23页码:3861-3871 |
| 关键词 | Cytokinesis Failure Fak Inhibitor Fluorescein Isothiocyanate Macrophage Multinuclear Cell Pro-tumoral Cytokine |
| DOI | 10.1002/1873-3468.12895 |
| 产权排序 | 1 |
| 文献子类 | Article |
| 英文摘要 | Macrophages are abundant in the tumor microenvironment. They are highly plastic and able to acquire pro-tumoral phenotypes in response to microenvironmental stimuli. When we treated RAW 264.7 macrophages with inhibitors of various oncogenic pathways, we found that the focal adhesion kinase (FAK) inhibitors PF573228 and TAE226 could induce cell multinucleation by suppressing furrowing and cytokinesis. This failure in cytokinesis involves Rac1, whose activity is elevated by FAK inhibitors, and the p21-activated kinases, comprising the downstream effectors of Rac. We also investigated the influence of cell multinucleation on macrophage physiology in RAW 264.7 cells. This is the first study to report that FAK inhibitors suppress furrow ingression and early cytokinesis. Of note, we found that FAK inhibitors caused a dramatic increase in pro-tumoral cytokines in multinuclear cells, suggesting the potential to convert macrophages into pro-tumoral phenotypes. |
| 学科主题 | Biochemistry & Molecular Biology ; Biophysics ; Cell Biology |
| 语种 | 英语 |
| 资助机构 | We thank Dr Han Kang (Sichuan University) for helping us with the live-cell imaging, as well as Dr Kexin Xie (Chengdu Institute of Biology) for assistance with the confocal microscopy. We would also like to thank Prof. Zhi-Xiong Xiao, Prof. Qintong Li and Prof. Chenghua Li (Sichuan University) for improving our manuscript. This work was supported by the Institute for Drug Discovery and Development, Chinese Academy of Sciences (no. CASIMM0420152013 and CASIMM0420151009). The funders had no involvement in the study design, data collection and analysis, nor in the manuscript preparation and the decision to publish. ; Institute for Drug Discovery and Development, Chinese Academy of Sciences [CASIMM0420152013, CASIMM0420151009] ; We thank Dr Han Kang (Sichuan University) for helping us with the live-cell imaging, as well as Dr Kexin Xie (Chengdu Institute of Biology) for assistance with the confocal microscopy. We would also like to thank Prof. Zhi-Xiong Xiao, Prof. Qintong Li and Prof. Chenghua Li (Sichuan University) for improving our manuscript. This work was supported by the Institute for Drug Discovery and Development, Chinese Academy of Sciences (no. CASIMM0420152013 and CASIMM0420151009). The funders had no involvement in the study design, data collection and analysis, nor in the manuscript preparation and the decision to publish. ; Institute for Drug Discovery and Development, Chinese Academy of Sciences [CASIMM0420152013, CASIMM0420151009] ; We thank Dr Han Kang (Sichuan University) for helping us with the live-cell imaging, as well as Dr Kexin Xie (Chengdu Institute of Biology) for assistance with the confocal microscopy. We would also like to thank Prof. Zhi-Xiong Xiao, Prof. Qintong Li and Prof. Chenghua Li (Sichuan University) for improving our manuscript. This work was supported by the Institute for Drug Discovery and Development, Chinese Academy of Sciences (no. CASIMM0420152013 and CASIMM0420151009). The funders had no involvement in the study design, data collection and analysis, nor in the manuscript preparation and the decision to publish. ; Institute for Drug Discovery and Development, Chinese Academy of Sciences [CASIMM0420152013, CASIMM0420151009] ; We thank Dr Han Kang (Sichuan University) for helping us with the live-cell imaging, as well as Dr Kexin Xie (Chengdu Institute of Biology) for assistance with the confocal microscopy. We would also like to thank Prof. Zhi-Xiong Xiao, Prof. Qintong Li and Prof. Chenghua Li (Sichuan University) for improving our manuscript. This work was supported by the Institute for Drug Discovery and Development, Chinese Academy of Sciences (no. CASIMM0420152013 and CASIMM0420151009). The funders had no involvement in the study design, data collection and analysis, nor in the manuscript preparation and the decision to publish. ; Institute for Drug Discovery and Development, Chinese Academy of Sciences [CASIMM0420152013, CASIMM0420151009] |
| 源URL | [http://210.75.237.14/handle/351003/29204]  |
| 专题 | 成都生物研究所_天然产物研究 |
| 通讯作者 | Chen, S (reprint author), Chinese Acad Sci, Chengdu Inst Biol, Chengdu 610041, Sichuan, Peoples R China. |
| 推荐引用方式 GB/T 7714 | He, X,Chen, X,Li, BG,et al. FAK inhibitors induce cell multinucleation and dramatically increase pro-tumoral cytokine expression in RAW 264.7 macrophages[J]. FEBS LETTERS,2017,591(23):3861-3871. |
| APA | He, X,Chen, X,Li, BG,Ji, JX,Chen, S,&Chen, S .(2017).FAK inhibitors induce cell multinucleation and dramatically increase pro-tumoral cytokine expression in RAW 264.7 macrophages.FEBS LETTERS,591(23),3861-3871. |
| MLA | He, X,et al."FAK inhibitors induce cell multinucleation and dramatically increase pro-tumoral cytokine expression in RAW 264.7 macrophages".FEBS LETTERS 591.23(2017):3861-3871. |
入库方式： OAI收割
来源：成都生物研究所
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