Altered Signaling Pathways in Prostate Cancer Drive Metabolic Fate

Abstract

Prostate cancer is one of the leading causes of men death worldwide. Several signaling pathways are highly implicated in the progression of this disease. Interestingly, variations in a single gene can orchestrate changes in a metabolic pathway and thus, confer an adaptive advantage. Metabolic reprogramming has emerged as one of the hallmarks of cancer and arises as consequence of changes in critical signaling pathways provoked by balance disruption between oncogenes and tumor suppressors expression. Therefore, metabolomic analyses provide relevant information that is not available with only genomic or proteomic studies. Noticeably, basal energetic status in luminal epithelial cells of the prostate gland contrasts with other tissues since Krebs cycle is altered so as to generate high citrate levels achieving a more glycolytic phenotype. Furthermore, the altered signaling pathways in prostate cancer depict changes in cellular metabolism that support the demands of rapid cell division. Particularly, metabolic pathways significantly altered in this malignancy are glutaminolysis and lipid metabolism that contribute directly to the production of acetyl-CoA and NADPH required for the synthesis of fatty acids. Therefore, deciphering the metabolic rewiring propelled by signaling pathways dysregulation is vital for the development of new therapeutic approaches in prostate cancer. Advances in these fields highlight the importance of changes in energetic metabolism during the progression to castration resistant prostate cancer and bone metastases.