Title | New strategies in prostate cancer: targeting lipogenic pathways and the energy sensor AMPK. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Zadra G, Priolo C, Patnaik A, Loda M |
Journal | Clin Cancer Res |
Volume | 16 |
Issue | 13 |
Pagination | 3322-8 |
Date Published | 2010 Jul 01 |
ISSN | 1557-3265 |
Keywords | AMP-Activated Protein Kinases, Dietary Fats, Energy Metabolism, Humans, Intracellular Signaling Peptides and Proteins, Lipogenesis, Male, Metabolic Syndrome, Obesity, Prostatic Neoplasms, Protein-Serine-Threonine Kinases, Signal Transduction, TOR Serine-Threonine Kinases |
Abstract | Although the role of metabolic syndrome (MS) and a high fat diet in prostate cancer (PCa) risk is still a matter of intense debate, it is becoming increasingly clear that obesity can cause perturbations in metabolic pathways that contribute to the pathogenesis and progression of PCa. Moreover, prostate epithelial cells per se undergo a series of metabolic changes, including an increase in de novo lipogenesis, during the process of tumor formation. These metabolic alterations, at both the cellular and organismal levels, are intertwined with genetic aberrations necessary for neoplastic transformation. Thus, altered metabolism is currently subject to intense research efforts and might provide preventative and therapeutic opportunities, as well as a platform for biomarker development. In this article, we review evidence that the metabolic sensor 5'-AMP-activated protein kinase (AMPK), which physiologically integrates nutritional and hormonal signals and regulates cell survival and growth-related metabolic pathways to preserve intracellular ATP levels, represents a link between energy homeostasis and cancer. Thus, when AMPK is not activated, as in the setting of MS and obesity, systemic metabolic alterations permissive to the development of PCa are allowed to proceed unchecked. Hence, the use of AMPK activators and inhibitors of key lipogenic enzymes may represent a promising therapeutic strategy for PCa. |
DOI | 10.1158/1078-0432.CCR-09-1955 |
Alternate Journal | Clin Cancer Res |
PubMed ID | 20423984 |
Grant List | P01CA89021 / CA / NCI NIH HHS / United States R01CA131945 / CA / NCI NIH HHS / United States P50 CA90381 / CA / NCI NIH HHS / United States |
Related Faculty:
Massimo Loda, M.D.