Metabolic changes during prostate cancer development and progression

Abstract

Metabolic reprogramming has been recognised as a hallmark in solid tumours. Malignant modification of the tumour’s bioenergetics provides energy for tumour growth and progression. Otto Warburg first reported these metabolic and biochemical changes in 1927. In prostate cancer (PCa) epithelial cells, the tumour metabolism also changes during development and progress. These alterations are partly driven by the androgen receptor, the key regulator in PCa development, progress, and survival. In contrast to other epithelial cells of different entities, glycolytic metabolism in prostate cells sustains physiological citrate secretion in the normal prostatic epithelium. In the early stages of PCa, citrate is utilised to power oxidative phosphorylation and fuel lipogenesis, enabling tumour growth and progression. In advanced and incurable castration-resistant PCa, a metabolic shift towards choline, amino acid, and glycolytic metabolism fueling tumour growth and progression has been described. Therefore, even if the metabolic changes are not fully understood, the altered metabolism during tumour progression may provide opportunities for novel therapeutic strategies, especially in advanced PCa stages. This review focuses on the main differences in PCa’s metabolism during tumourigenesis and progression highlighting glutamine’s role in PCa.

Investigate the impact of ICAM-2 and Neprilysin biomarkers in prostate cancer patients infected with JC virus in AL-Najaf AL-Ashraf Province

“…The increased neprilysin levels observed in individuals with JCV infection could indicate a possible link between JCV infection and modified neprilysin expression in prostate cancer [35,36]. Neprilysin, an enzyme responsible for breaking down peptides which including those linked to tumor growth and spread and may therefore play a role in the advancement or severity of prostate cancer in JCV-infected individuals [37,38] and the possibility exists that JCV infection could trigger the increase in neprilysin levels, either through direct interactions with viral proteins or immune responses activated by the infection [39]. Elevated levels of neprilysin in prostate cancer patients infected with JCV could potentially function as a biomarker indicating disease aggressiveness or prognosis [40,41].…”

Transcending frontiers in prostate cancer: the role of oncometabolites on epigenetic regulation, CSCs, and tumor microenvironment to identify new therapeutic strategies

“…On the other hand, in the first steps of prostate carcinogenesis, tumor cells become citrate-dependent, increasing OXPHOS and lipogenesis. In the CRPC, choline, amino acid, and glycolytic metabolism are promoted more than OXPHOS [ 92 ]. Thus, the different metabolic requirements along PC progression alter the TME, being the mitochondria at the center of the crosstalk.…”

Integrative Metabolomic Analysis of Serum and Selected Serum Exosomal microRNA in Metastatic Castration-Resistant Prostate Cancer

“…The progression of PC involves a decrease in zinc concentrations, leading to the reactivation of m-aconitase and the initiation of citrate oxidation through the TCA cycle [ 14 ]. In contrast to many tissues in the human body, the metabolism of primary PC cells is characterized by high lipogenesis, lower glycolysis, and dependence on oxidative phosphorylation [ 15 ]. Consequently, citrate can be exported to the cytoplasm and converted back into acetyl-CoA for de novo synthesis of fatty acids and cholesterol [ 16 ].…”