Peroxisomes and the Malignant Potential of Prostate Cancer Cells.

Prostate cancer (PCa) is the second most common cancer and fifth leading cause of cancer death among men worldwide. Intriguingly, primary prostate tumors do not undergo a metabolic switch from oxidative phosphorylation to aerobic glycolysis to meet increased energetic and biosynthetic demand for cell growth and division. In contrast, PCa cells preferentially use fatty acids for metabolic fuel, and malignant transformation of prostate tissue is accompanied by a sustained increase in the activity of both lipogenic and oxidative enzymes. As peroxisomes (PO) play a key role in cellular lipid and redox metabolism, it may not come as a surprise that these organelles are increasingly recognized as being involved in the pathogenesis of PCa. However, many uncertainties and inadequacies in our understanding of how PO function in PCa progression remain. This project is intended to gain a more coherent picture of how alterations in PO metabolism contribute to PCa development, progression, and therapy response. Specifically, by employing cutting-edge technologies, we will (i) systematically inventory which peroxisomal parameters are affected in commonly used cell models of PCa, (ii) investigate whether or not the observed alterations can be causally linked to PCa malignancy, and (iii) search for evidence in favor of or against the idea that alterations in PO metabolism can be exploited for PCa therapy. As such, the outcome of this project may be of interest to PCa patients, their families, and health care providers.