Submicron silica particles drives prostate cancer aggressiveness via lipid-metabolic reprogramming

Abstract

Micron-sized (1 µm - 100 µm) and submicron-sized (100 nm–1 µm) silica particles are prevalent in both natural environments and areas influenced by human activities. Their environmental forms, origins, and pathways of human exposure differ markedly from those of nanoscale silica. Empirical studies have demonstrated that silica can induce cellular oxidative stress and mitochondrial dysfunction, as well as inhibit the activity of key enzymes in the tricarboxylic acid (TCA) cycle, such as isocitrate dehydrogenase. This inhibition can promote tumor cell proliferation and invasion. Furthermore, silica may activate the HIF-1α/mTOR signaling axis, leading to the upregulation of glucose transporter GLUT1 and lactate dehydrogenase (LDHA), thereby enhancing glycolytic metabolic flux. Concurrently, it may inhibit fatty acid β-oxidation, resulting in abnormal lipid accumulation and the promotion of pro-inflammatory mediator release. In summary, the accumulation of submicron silica within the bodies of cancer patients has the potential to induce metabolic disorders. Such metabolic reprogramming may influence the progression of prostate cancer (PCa) and adversely impact postoperative quality of life. In this study, we demonstrated that prolonged exposure of the lungs to submicron silica particles can induce alterations in lipid metabolism in PCa and significantly enhance the proliferation and invasive capacity of PCa cells. Consequently, elucidating the mechanisms underlying silica-induced metabolic imbalance holds substantial clinical significance for enhancing the prognosis of patients with tumors related to exposure.