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The androgen receptor fuels prostate cancer by regulating central metabolism and biosynthesis.

Authors :
Massie, Charles E
Lynch, Andy
Ramos-Montoya, Antonio
Boren, Joan
Stark, Rory
Fazli, Ladan
Warren, Anne
Scott, Helen
Madhu, Basetti
Sharma, Naomi
Bon, Helene
Zecchini, Vinny
Smith, Donna-Michelle
DeNicola, Gina M
Mathews, Nik
Osborne, Michelle
Hadfield, James
MacArthur, Stewart
Adryan, Boris
Lyons, Scott K
Source :
EMBO Journal; 7/6/2011, Vol. 30 Issue 13, p2719-2733, 15p, 3 Diagrams, 3 Graphs
Publication Year :
2011

Abstract

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
02614189
Volume :
30
Issue :
13
Database :
Complementary Index
Journal :
EMBO Journal
Publication Type :
Academic Journal
Accession number :
62248592
Full Text :
https://doi.org/10.1038/emboj.2011.158