A tightly controlled Src-YAP signaling axis determines therapeutic response to dasatinib in renal cell carcinoma
文献类型：期刊论文
| 作者 | Sun, Jingya1,2; Wang, Xin1,2 ; Tang, Boyun3; Liu, Hongchun1,2; Zhang, Minmin1,2; Wang, Yueqin1,2; Ping, Fangfang1,2; Ding, Jian1,2; Shen, Aijun1,2; Geng, Meiyu1,2
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| 刊名 | THERANOSTICS
 |
| 出版日期 | 2018 |
| 卷号 | 8期号:12页码:3256-3267 |
| 关键词 | dasatinib YAP Src renal cell carcinoma |
| ISSN号 | 1838-7640 |
| DOI | 10.7150/thno.23964 |
| 文献子类 | Article |
| 英文摘要 | Over the past decade, therapies targeting the VEGF/VEGFR and mTOR pathways have served as the standard of care for the clinical management of renal cell carcinoma (RCC) patients. Albeit promising, these targeted drugs have attained only modest clinical benefits with limited prolonged progression-free survival. Therefore, alternative reasonable and applicable therapeutic approaches should be introduced to improve the clinical outcome of RCC patients. Methods: FDA approved kinase inhibitors were screened to evaluate their abilities to suppress the proliferation of RCC cells. Then, the downstream effector, therapeutic target and signaling pathway of the selected drug were identified by gene expression array, RNAi, kinase profile and rescue verification. Finally, the in vivo effectiveness of the drug was assessed in cell line-based xenograft models and patient-derived xenograft models. Results: In this study, we discovered that dasatinib is a potent agent that can impair RCC cell viability in vitro and decrease tumor growth in vivo. Mechanistically, we improved the understanding of the precise mechanistic role of YAP as a pivotal effector of dasatinib-induced anti-proliferation through Src-JNK-LIMD1 -LATS signaling cascade in RCC cells. Meanwhile, our results indicated that the alteration of p-YAP is closely correlated to the growth inhibition caused by dasatinib in sensitive RCC models. Conclusion: Our findings provide evidence that dasatinib may serve as a powerful drug candidate to treat subgroups of RCC patients with hyper-activated Src-YAP signaling axis, and the alteration of p-YAP could serve as a functional response biomarker of dasatinib in RCC. |
| WOS关键词 | ABL INHIBITORS IMATINIB ; PHASE-III TRIAL ; TARGETED THERAPY ; INTERFERON-ALPHA ; DOUBLE-BLIND ; CANCER ; RESISTANCE ; PATHWAY ; EVEROLIMUS ; SUNITINIB |
| 资助项目 | National Natural Science Foundation of China[81402966] ; National Natural Science Foundation of China[81673472] ; National Natural Science Foundation of China[91229205] ; National Program on Key Basic Research Project of China[2012CB910704] ; Natural Science Foundation of China for Innovation Research Group[81321092] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development[00000000] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020101] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020105] |
| WOS研究方向 | Research & Experimental Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:000432355000007 |
| 出版者 | IVYSPRING INT PUBL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272315]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 分子影像中心（筹） |
| 通讯作者 | Ding, Jian; Shen, Aijun; Geng, Meiyu |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 3.Gene Co Ltd, Shanghai 200233, Peoples R China |
| 推荐引用方式 GB/T 7714 | Sun, Jingya,Wang, Xin,Tang, Boyun,et al. A tightly controlled Src-YAP signaling axis determines therapeutic response to dasatinib in renal cell carcinoma[J]. THERANOSTICS,2018,8(12):3256-3267. |
| APA | Sun, Jingya.,Wang, Xin.,Tang, Boyun.,Liu, Hongchun.,Zhang, Minmin.,...&Geng, Meiyu.(2018).A tightly controlled Src-YAP signaling axis determines therapeutic response to dasatinib in renal cell carcinoma.THERANOSTICS,8(12),3256-3267. |
| MLA | Sun, Jingya,et al."A tightly controlled Src-YAP signaling axis determines therapeutic response to dasatinib in renal cell carcinoma".THERANOSTICS 8.12(2018):3256-3267. |
入库方式： OAI收割
来源：上海药物研究所
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