Leptin signalling, obesity and prostate cancer: molecular and clinical perspective on the old dilemma
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Heba Alshaker1,2, Keith Sacco3, Albandri Alfraidi1, Aun Muhammad1, Mathias Winkler1 and Dmitri Pchejetski4
1 Department of Surgery and Cancer, Imperial College London, London, UK
2 Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, Petra University, Amman, Jordan
3 University of Malta Medical School, Mater Dei Hospital, Tal-Qroqq, MSD, Malta
4 School of Medicine, University of East Anglia, Norwich, UK
Heba Alshaker, email:
Keywords: obesity, BMI, prostate cancer, mortality, progression, adipokine, leptin, therapy
Received: July 15, 2015 Accepted: August 16, 2015 Published: September 10, 2015
The prevalence of global obesity is increasing. Obesity is associated with general cancer-related morbidity and mortality and is a known risk factor for development of specific cancers. A recent large systematic review of 24 studies based on meta-analysis of 11,149 patients with prostate cancer showed a significant correlation between obesity and the risk of advanced prostate cancer. Further, a sustained reduction in BMI correlates with a decreased risk of developing aggressive disease. On the other hand, the correlation between consuming different products and prostate cancer occurrence/risk is limited.
Here, we review the role of adipose tissue from an endocrine perspective and outline the effect of adipokines on cancer metabolism, with particular focus on leptin. Leptin exerts its physiological and pathological effects through modification of intracellular signalling, most notably activating the Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 pathway and recently shown sphingolipid pathway. Both high levels of leptin in circulation and leptin receptor mutation are associated with prostate cancer risk in human patients; however, the in vivo mechanistic evidence is less conclusive.
Given the complexity of metabolic cancer pathways, it is possible that leptin may have varying effects on prostate cancer at different stages of its development, a point that may be addressed by further epidemiological studies.
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