Ablation of the oncogenic transcription factor ERG by deubiquitinase inhibition in prostate cancer
Abstract
The transcription factor E-twenty-six related gene (ERG) is a major driver of prostate cancer, which makes this protein an interesting target for drug development. In this study, we report the discovery of an enzyme, ubiquitin-specific peptidase 9, X-linked (USP9X), which stabilizes ERG. We demonstrate that inhibition of USP9X with the small molecule WP1130 causes rapid degradation of ERG and blocked the growth of cultured prostate cancer cells and prostate tumors that express ERG. These findings suggest that inhibition of USP9X with small molecules should be explored for the development of a prostate cancer therapy that targets ERG.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- March 2014
- DOI:
- 10.1073/pnas.1322198111
- Bibcode:
- 2014PNAS..111.4251W