Lipid metabolism in prostate cancer.
The malignant transformation of cells requires adaptations across multiple metabolic processes to satisfy the energy required for their increased rate of proliferation. Dysregulation of lipid metabolism has been a hallmark of the malignant phenotype; increased lipid accumulation secondary to changes in the levels of a variety of lipid metabolic enzymes has been documented in a variety of tumors, including prostate. Alterations in prostate lipid metabolism include upregulation of several lipogenic enzymes as well as of enzymes that function to oxidize fatty acids as an energy source. Cholesterol metabolism and phospholipid metabolism are also affected. With respect to lipogenesis, most studies have concentrated on increased expression and activity ofthe de novo fatty acid synthesis enzyme, fatty acid synthase (FASN), with suggestions that FASN might function as an oncogene. A central role for fatty acid oxidation in supplying energy to the prostate cancer cell is supported by the observation that the peroxisomal enzyme, α-methylacyl-CoA racemase (AMACR), which facilitates the transformation of branched chain fatty acids to a form suitable for β-oxidation, is highly overexpressed in prostate cancer compared with normal prostate. Exploitation of the alterations in lipid metabolic pathways in prostate cancer could result in the development of new therapeutic modalities as well as provide candidates for new prognostic and predictive biomarkers. AMACR has already proven to be a valuable biomarker in distinguishing normal from malignant prostate tissue, and is used routinely in clinical practice.
Department of Pathology,Physiology, New York University School of Medicine New York, NY, USA.
Xinyu
X
Wu
Department of Pathology,Physiology, New York University School of Medicine New York, NY, USA.
Garrett
G
Daniels
Department of Pathology,Physiology, New York University School of Medicine New York, NY, USA ; VA New York Harbor Healthcare System New York, NY, USA.
Peng
P
Lee
VA New York Harbor Healthcare System New York, NY, USA ; Department of Neuroscience & Physiology, New York University School of Medicine New York, NY, USA.
Marie E
ME
Monaco
Prostate cancer; fatty acid oxidation; lipogenesis