Increased transcriptional and metabolic capacity for lipid metabolism in the peripheral zone of the prostate may underpin its increased susceptibility to cancer
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Omar Al Kadhi1,2,*, Maria H. Traka1,*, Antonietta Melchini1, Perla Troncoso-Rey3, Wiktor Jurkowski3, Marianne Defernez4, Purnima Pachori5, Robert D. Mills2, Richard Y. Ball6 and Richard F. Mithen1
1Food and Health Programme, Quadram Institute Bioscience, Norwich, UK
2Department of Urology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
3Integrative Genomics, Earlham Institute, Norwich, UK
4Analytical Sciences Unit, Quadram Institute Bioscience, Norwich, UK
5Platforms and Pipelines Bioinformatics, Earlham Institute, Norwich, UK
6Norfolk and Waveney Cellular Pathology Service, Norfolk and Norwich University Hospital, Norwich, UK
*These authors contributed equally to the work
Richard F. Mithen, email: [email protected]
Keywords: metabolism, fatty acid metabolism, steroid biosynthesis, prostate zones, prostate cancer
Received: September 18, 2016 Accepted: May 02, 2017 Published: May 17, 2017
The human prostate gland comprises three distinct anatomical glandular zones, namely the peripheral, central and transitional zones. Although prostate cancer can arise throughout the prostate, it is more frequent in the peripheral zone. In contrast, hyperplasia occurs most frequently in the transitional zone. In this paper, we test the hypothesis that peripheral and transitional zones have distinct metabolic adaptations that may underlie their different inherent predispositions to cancer and hyperplasia. In order to do this, we undertook RNA sequencing and high-throughput metabolic analyses of non-cancerous tissue from the peripheral and transitional zones of patients undergoing prostatectomy. Integrated analysis of RNAseq and metabolomic data revealed that transcription of genes involved in lipid biosynthesis is higher in the peripheral zone, which was mirrored by an increase in fatty acid metabolites, such as lysolipids. The peripheral zone also exhibited increased fatty acid catabolic activity and contained higher level of neurotransmitters. Such increased capacity for de novo lipogenesis and fatty acid oxidation, which is characteristic of prostate cancer, can potentially provide a permissive growth environment within the peripheral zone for cancer growth and also transmit a metabolic growth advantage to newly emerging clones themselves. This lipo-rich priming may explain the observed susceptibility of the peripheral zone to oncogenesis.
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