| Literature DB >> 24656772 |
Guoqiang Li1, Weimin Ci2, Subhradip Karmakar3, Ke Chen4, Ruby Dhar3, Zhixiang Fan5, Zhongqiang Guo6, Jing Zhang4, Yuwen Ke4, Lu Wang1, Min Zhuang7, Shengdi Hu8, Xuesong Li9, Liqun Zhou9, Xianghong Li10, Matthew F Calabrese11, Edmond R Watson11, Sandip M Prasad12, Carrie Rinker-Schaeffer12, Scott E Eggener12, Thomas Stricker13, Yong Tian8, Brenda A Schulman14, Jiang Liu15, Kevin P White16.
Abstract
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.Entities:
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Year: 2014 PMID： 24656772 PMCID： PMC4443692 DOI： 10.1016/j.ccr.2014.02.007
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743