SPOP promotes tumorigenesis by acting as a key regulatory hub in kidney cancer

Guoqiang Li, Weimin Ci, Subhradip Karmakar, Ke Chen, Ruby Dhar, Zhixiang Fan, Zhongqiang Guo, Jing Zhang, Yuwen Ke, Lu Wang, Min Zhuang, Shengdi Hu, Xuesong Li, Liqun Zhou, Xianghong Li, Matthew F. Calabrese, Edmond R. Watson, Sandip M. Prasad, Carrie Rinker-Schaeffer, Scott E. EggenerThomas Stricker, Yong Tian, Brenda A. Schulman, Jiang Liu, Kevin P. White

Research output: Contribution to journalArticlepeer-review

147 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)455-468
Number of pages14
JournalCancer Cell
Volume25
Issue number4
DOIs
StatePublished - Apr 14 2014
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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