Axl inhibitor R428 induces apoptosis of cancer cells by blocking lysosomal acidification and recycling independent of Axl inhibition
文献类型：期刊论文
| 作者 | Chen, Fangfang1,2; Song, Qiaoling1,2; Yu, Qiang1,2
|
| 刊名 | AMERICAN JOURNAL OF CANCER RESEARCH
 |
| 出版日期 | 2018 |
| 卷号 | 8期号:8页码:1466-+ |
| 关键词 | R428 Axl cancer cells apoptosis autophagy vacuolization |
| ISSN号 | 2156-6976 |
| 文献子类 | Article |
| 英文摘要 | R428 (BGB324) is an anti-cancer drug candidate under clinical investigation. It inhibits the receptor tyrosine kinase Axl and induces apoptosis of many types of cancer cells, but the relationship between the two has not been well established. We investigated the molecular mechanisms of the R428-induced apoptosis and found that R428 induced extensive cytoplasmic vacuolization and caspase activation, independent of its inhibitory effects on Axl. Further analyses revealed that R428 blocked lysosomal acidification and recycling, accumulated autophagosomes and lysosomes, and induced cell apoptosis. Inhibition of autophagy by autophagy inhibitors or autophagic gene-knockout alleviated the R428-induced vacuoles formation and cell apoptosis. Our study uncovered a novel function and mechanism of R428 in addition to its ability to inhibit Axl. These data will help to better direct the application of R428 as an anti-cancer reagent. It also adds new knowledge to understand the regulation of autophagy and apoptosis. |
| WOS关键词 | HUMAN NEUROBLASTOMA-CELLS ; AUTOPHAGY ; DEGRADATION ; METASTASIS ; SURVIVAL ; KINASE ; GROWTH ; GENE |
| 资助项目 | National Natural Science Foundation of China[81673465] ; National Natural Science Foundation of China[81373447] ; China Ministry of Science and Technology Key New Drug Creation and Manufacturing Program[2014ZX09102001-002] ; China National Key Basic Research Program[2013CB910904] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000443206500010 |
| 出版者 | E-CENTURY PUBLISHING CORP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272299]  |
| 专题 | 药理学第一研究室 |
| 通讯作者 | Yu, Qiang |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd,Room 2-225, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Chen, Fangfang,Song, Qiaoling,Yu, Qiang. Axl inhibitor R428 induces apoptosis of cancer cells by blocking lysosomal acidification and recycling independent of Axl inhibition[J]. AMERICAN JOURNAL OF CANCER RESEARCH,2018,8(8):1466-+. |
| APA | Chen, Fangfang,Song, Qiaoling,&Yu, Qiang.(2018).Axl inhibitor R428 induces apoptosis of cancer cells by blocking lysosomal acidification and recycling independent of Axl inhibition.AMERICAN JOURNAL OF CANCER RESEARCH,8(8),1466-+. |
| MLA | Chen, Fangfang,et al."Axl inhibitor R428 induces apoptosis of cancer cells by blocking lysosomal acidification and recycling independent of Axl inhibition".AMERICAN JOURNAL OF CANCER RESEARCH 8.8(2018):1466-+. |
入库方式： OAI收割
来源：上海药物研究所
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