Journal
EMBO JOURNAL
Volume 30, Issue 13, Pages 2719-2733Publisher
WILEY
DOI: 10.1038/emboj.2011.158
Keywords
androgen receptor; chromatin; metabolism; prostate cancer; transcription
Categories
Funding
- NIHR Cambridge Biomedical Research Centre
- DOH HTA
- MRC
- CRUK
- University of Cambridge
- Cancer Research UK
- Hutchison Whampoa Limited
- MRC [G0900871] Funding Source: UKRI
- Cancer Research UK [19556, 11562] Funding Source: researchfish
- Medical Research Council [G0900871] Funding Source: researchfish
- Novo Nordisk Fonden [NNF11OC1014864] Funding Source: researchfish
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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. The EMBO Journal (2011) 30, 2719-2733. doi:10.1038/emboj.2011.158; Published online 20 May 2011
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