These authors contributed equally to this work
The androgen receptor fuels prostate cancer by regulating central metabolism and biosynthesis
Article first published online: 20 MAY 2011
Copyright © 2011 European Molecular Biology Organization
The EMBO Journal
Volume 30, Issue 13, pages 2719–2733, July 6, 2011
How to Cite
Massie, C. E., Lynch, A., Ramos-Montoya, A., Boren, J., Stark, R., Fazli, L., Warren, A., Scott, H., Madhu, B., Sharma, N., Bon, H., Zecchini, V., Smith, D.-M., DeNicola, G. M., Mathews, N., Osborne, M., Hadfield, J., MacArthur, S., Adryan, B., Lyons, S. K., Brindle, K. M., Griffiths, J., Gleave, M. E., Rennie, P. S., Neal, D. E. and Mills, I. G. (2011), The androgen receptor fuels prostate cancer by regulating central metabolism and biosynthesis. The EMBO Journal, 30: 2719–2733. doi: 10.1038/emboj.2011.158
There is a Have you seen? (July 2011) associated with this Article.
- Issue published online: 6 JUL 2011
- Article first published online: 20 MAY 2011
- Manuscript Accepted: 21 APR 2011
- Manuscript Received: 3 NOV 2010
- androgen receptor;
- prostate cancer;
The androgen receptor (AR) is a key regulator of prostate growth and the principal drug target for the treatment of prostate cancer. Previous studies have mapped AR targets and identified some candidates which may contribute to cancer progression, but did not characterize AR biology in an integrated manner. In this study, we took an interdisciplinary approach, integrating detailed genomic studies with metabolomic profiling and identify an anabolic transcriptional network involving AR as the core regulator. Restricting flux through anabolic pathways is an attractive approach to deprive tumours of the building blocks needed to sustain tumour growth. Therefore, we searched for targets of the AR that may contribute to these anabolic processes and could be amenable to therapeutic intervention by virtue of differential expression in prostate tumours. This highlighted calcium/calmodulin-dependent protein kinase kinase 2, which we show is overexpressed in prostate cancer and regulates cancer cell growth via its unexpected role as a hormone-dependent modulator of anabolic metabolism. In conclusion, it is possible to progress from transcriptional studies to a promising therapeutic target by taking an unbiased interdisciplinary approach.