IR@PKUHSC  > 北京大学第一临床医学院  > 泌尿外科
学科主题临床医学
SPOP Promotes Tumorigenesis by Acting as a Key Regulatory Hub in Kidney Cancer
Li, Guoqiang1,3; Ci, Weimin2; Karmakar, Subhradip4,5,6; Chen, Ke1; Dhar, Ruby4,5,6; Fan, Zhixiang10; Guo, Zhongqiang1,11; Zhang, Jing1; Ke, Yuwen1; Wang, Lu1,3; Zhuang, Min13; Hu, Shengdi14; Li, Xuesong11; Zhou, Liqun11; Li, Xianghong12; Calabrese, Matthew F.15; Watson, Edmond R.15; Prasad, Sandip M.8; Rinker-Schaeffer, Carrie8; Eggener, Scott E.8; Stricker, Thomas4,5,9; Tian, Yong14; Schulman, Brenda A.15,16; Liu, Jiang1; White, Kevin P.4,5,6,7
刊名CANCER CELL
2014-04-14
DOI10.1016/j.ccr.2014.02.007
25期:4页:455-468
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology ; Cell Biology
研究领域[WOS]Oncology ; Cell Biology
关键词[WOS]RENAL-CELL CARCINOMA ; PTEN TUMOR-SUPPRESSOR ; UBIQUITIN-LIGASE ; PHOSPHATASE-ACTIVITY ; INTERFERON-ALPHA ; PROTEIN ; PATHWAY ; PHOSPHORYLATION ; EXPRESSION ; HYPOXIA
英文摘要

Hypoxic stress and hypoxia-inducible factors (HIFs) play important roles in a wide range of tumors. We demonstrate that SPOP, which encodes an E3 ubiquitin ligase component, is a direct transcriptional target of HIFs in clear cell renal cell carcinoma (ccRCC). Furthermore, hypoxia results in cytoplasmic accumulation of SPOP, which is sufficient to induce tumorigenesis. This tumorigenic activity occurs through the ubiquitination and degradation of multiple regulators of cellular proliferation and apoptosis, including the tumor suppressor PTEN, ERK phosphatases, the proapoptotic molecule Daxx, and the Hedgehog pathway transcription factor Gli2. Knockdown of SPOP specifically kills ccRCC cells, indicating that it may be a promising therapeutic target. Collectively, our results indicate that SPOP serves as a regulatory hub to promote ccRCC tumorigenesis.

语种英语
WOS记录号WOS:000334568400007
项目编号2011CB510101 ; 2014AA020608 ; 81101940 ; 91231112 ; 31171244 ; 81171902 ; DRG 2021-9 ; 5R01GM069530 ; 5P30CA021765 ; CAS grant 09CF011001 ; 2011CB510101 ; 5102031 ; P50GM081892
资助机构Ministry of Science and Technology (MOST) 973 Program ; National 863 High-Tech Foundation ; National Science Foundation of China (NSFC) ; NSFC ; Howard Hughes Medical Institute (HHMI) postdoctoral fellowship from the Damon Runyon Cancer Research Foundation ; National Research Service Award from the NIH ; ALSAC ; HHMI ; NIH ; CAS grant ; MOST 973 Program ; Beijing Science Foundation ; W.M. Keck Foundation ; United States National Institute of General Medical Sciences ; Chicago Community Trust from the Chicago Biomedical Consortium
引用统计
被引频次:52[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62160
专题北京大学第一临床医学院_泌尿外科
作者单位1.Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA
2.Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA
3.Univ Chicago, Dept Med, Med Genet Sect, Chicago, IL 60637 USA
4.Univ Chicago, Dept Surg, Urol Sect, Chicago, IL 60637 USA
5.Univ Chicago, Dept Pathol, Chicago, IL 60637 USA
6.Kunming Med Univ, Kunming 650500, Yunnan, Peoples R China
7.Peking Univ, Hosp 1, Dept Urol, Beijing 100034, Peoples R China
8.Chinese Acad Sci, Beijing Inst Genom, Key Lab Genome Sci & Informat, Beijing 100101, Peoples R China
9.Chinese Acad Sci, Beijing Inst Genom, Lab Dis Genom & Individualized Med, Beijing 100101, Peoples R China
10.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
11.Argonne Natl Lab, Chicago, IL 60637 USA
12.Peking Univ, Canc Hosp, Dept Pathol, Beijing 100142, Peoples R China
13.Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA
14.Chinese Acad Sci, Inst Biophys, Lab Anim Res Ctr, Beijing 100101, Peoples R China
15.St Jude Childrens Res Hosp, Dept Biol Struct, Memphis, TN 38105 USA
16.St Jude Childrens Res Hosp, Howard Hughes Med Inst, Memphis, TN 38105 USA
推荐引用方式
GB/T 7714
Li, Guoqiang,Ci, Weimin,Karmakar, Subhradip,et al. SPOP Promotes Tumorigenesis by Acting as a Key Regulatory Hub in Kidney Cancer[J]. CANCER CELL,2014,25(4):455-468.
APA Li, Guoqiang.,Ci, Weimin.,Karmakar, Subhradip.,Chen, Ke.,Dhar, Ruby.,...&White, Kevin P..(2014).SPOP Promotes Tumorigenesis by Acting as a Key Regulatory Hub in Kidney Cancer.CANCER CELL,25(4),455-468.
MLA Li, Guoqiang,et al."SPOP Promotes Tumorigenesis by Acting as a Key Regulatory Hub in Kidney Cancer".CANCER CELL 25.4(2014):455-468.
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