FBW7 is associated with prognosis, inhibits malignancies and enhances temozolomide sensitivity in glioblastoma cells
文献类型：期刊论文
| 作者 | Lin, Jing9; Ji, Aihui8; Qiu, Guanzhong7; Feng, Huaizhi6; Li, Jian5; Li, Shuo6; Zou, Yongxiang4; Cui, Yong1; Song, Chaoli9; He, Hua3,8 |
| 刊名 | CANCER SCIENCE
 |
| 出版日期 | 2018-04 |
| 卷号 | 109期号:4页码:1001-1011 |
| 关键词 | Aurora B FBW7 glioma Mcl1 temozolomide |
| ISSN号 | 1349-7006 |
| DOI | 10.1111/cas.13528 |
| 文献子类 | Article |
| 英文摘要 | F-box and WD repeat domain-containing 7 (FBW7) is a SCF-type E3 ubiquitin ligase targeting a multitude of oncoproteins for degradation. Acting as one of the most important tumor suppressors, it is frequently inactivated in various tumors. In this study we aimed to evaluate the relationship of FBW7 with glioma pathology and prognosis, and examine its effect in glioma malignancies and temozolomide (TMZ)-based therapy. Clinical tissues and TCGA database analysis revealed that FBW7 expression was correlated inversely with glioma histology and positively with patient survival time. Lentivirus transfection-induced FBW7 overexpression significantly suppressed proliferation, invasion and migration of U251 and U373 cells, whereas knockdown of FBW7 by targeted shRNA promoted proliferation, invasion and migration of glioma cells. Most importantly, the expression level of FBW7 was found to affect the 50% inhibitory concentration (IC50) of U251 and the TMZ-resistant variant. Combining TMZ with FBW7 overexpression notably increased the cytotoxicity compared to TMZ treatment alone, which was conversely attenuated by FBW7 knockdown. Moreover, flow cytometry (FC) analysis showed overexpression of FBW7, TMZ or the combination-increased proportion of G2/M arrest and the apoptotic rate, whereas FBW7 inhibition reduced G2/M arrest and apoptosis in U251 cells. Finally, mechanistic study found that FBW7 overexpression downregulated Aurora B, Mcl1 and Notch1 levels in a time-dependent pattern and this expressional suppression was independent of TMZ. These findings collectively demonstrate the critical role of FBW7 as a prognostic factor and a potential target to overcome chemoresistance of glioblastoma. |
| WOS关键词 | HUMAN GLIOMA-CELLS ; TUMOR-SUPPRESSOR ; DEPENDENT DEGRADATION ; INDUCED CYTOTOXICITY ; UBIQUITIN LIGASES ; CANCER ; FBXW7 ; APOPTOSIS ; PHOSPHORYLATION ; METASTASIS |
| 资助项目 | National Natural Science Foundation[30930094] ; National Natural Science Foundation[81302187] ; National Natural Science Foundation[81702944] ; Ministry of Health of the People's Liberation Army[CWS14C063] ; State Key Laboratory of Drug Research[SIMM1705KF-10] ; Medical Project of Sichuan Province Medical Association[S15005] ; Special Presidential Foundation of General Hospital of Jinan Military Command[2016BS04] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000429411800013 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279826]  |
| 专题 | 新药研究国家重点实验室 中科院受体结构与功能重点实验室 |
| 通讯作者 | Song, Chaoli; He, Hua; Lu, Yicheng |
| 作者单位 | 1.Peoples Liberty Army, Hosp 411, Dept Neurosurg, Shanghai, Peoples R China; 2.Second Mil Med Univ, Changzheng Hosp, Dept Neurosurg, Shanghai, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State key Lab Drug Res, Beijing, Peoples R China; 4.Peoples Liberty Army, Hosp 463, Dept Neurosurg, Shenyang, Liaoning, Peoples R China; 5.452 Hosp Western Air Force, Dept Urol, Chengdu, Sichuan, Peoples R China; 6.452 Hosp Western Air Force, Dept Nutr, Chengdu, Sichuan, Peoples R China; 7.Jinan Mil Command, Gen Hosp, Dept Neurosurg, Jinan, Shandong, Peoples R China; 8.Shandong Prov Western Hosp, Dept Rehabil Med, Jinan, Shandong, Peoples R China; 9.452 Hosp Western Air Force, Dept Neurosurg, Chengdu, Sichuan, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Lin, Jing,Ji, Aihui,Qiu, Guanzhong,et al. FBW7 is associated with prognosis, inhibits malignancies and enhances temozolomide sensitivity in glioblastoma cells[J]. CANCER SCIENCE,2018,109(4):1001-1011. |
| APA | Lin, Jing.,Ji, Aihui.,Qiu, Guanzhong.,Feng, Huaizhi.,Li, Jian.,...&Lu, Yicheng.(2018).FBW7 is associated with prognosis, inhibits malignancies and enhances temozolomide sensitivity in glioblastoma cells.CANCER SCIENCE,109(4),1001-1011. |
| MLA | Lin, Jing,et al."FBW7 is associated with prognosis, inhibits malignancies and enhances temozolomide sensitivity in glioblastoma cells".CANCER SCIENCE 109.4(2018):1001-1011. |
入库方式： OAI收割
来源：上海药物研究所
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