TY - JOUR
T1 - SPOP promotes tumorigenesis by acting as a key regulatory hub in kidney cancer
AU - Li, Guoqiang
AU - Ci, Weimin
AU - Karmakar, Subhradip
AU - Chen, Ke
AU - Dhar, Ruby
AU - Fan, Zhixiang
AU - Guo, Zhongqiang
AU - Zhang, Jing
AU - Ke, Yuwen
AU - Wang, Lu
AU - Zhuang, Min
AU - Hu, Shengdi
AU - Li, Xuesong
AU - Zhou, Liqun
AU - Li, Xianghong
AU - Calabrese, Matthew F.
AU - Watson, Edmond R.
AU - Prasad, Sandip M.
AU - Rinker-Schaeffer, Carrie
AU - Eggener, Scott E.
AU - Stricker, Thomas
AU - Tian, Yong
AU - Schulman, Brenda A.
AU - Liu, Jiang
AU - White, Kevin P.
N1 - Funding Information:
We thank Erin E. Mowers for critical reading and editing of the manuscript. W.C. was supported by grant 2011CB510101 from the Ministry of Science and Technology (MOST) 973 Program. K.Y. was supported by the National 863 High-Tech Foundation (grant 2014AA020608). K.C. was supported by National Science Foundation of China (NSFC) grant 81101940. W.C. was supported by NSFC grants 91231112 and 31171244. M.C. was supported by a Howard Hughes Medical Institute (HHMI) postdoctoral fellowship from the Damon Runyon Cancer Research Foundation (DRG 2021-9). T.S. was supported by a National Research Service Award from the NIH. B.S. was supported by ALSAC, the HHMI, NIH grant 5R01GM069530, and NIH grant 5P30CA021765. Y.T. was supported by CAS grant 09CF011001. J.L. was supported by the MOST 973 Program (2011CB510101), NSFC grant 81171902, and Beijing Science Foundation grant 5102031. K.P.W. was supported by the W.M. Keck Foundation, the United States National Institute of General Medical Sciences grant P50GM081892 and by the Searle Funds at The Chicago Community Trust from the Chicago Biomedical Consortium.
PY - 2014/4/14
Y1 - 2014/4/14
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ccr.2014.02.007
DO - 10.1016/j.ccr.2014.02.007
M3 - Article
C2 - 24656772
AN - SCOPUS:84898539268
SN - 1535-6108
VL - 25
SP - 455
EP - 468
JO - Cancer Cell
JF - Cancer Cell
IS - 4
ER -