University of Würzburg, Institute of Anatomy and Cell Biology, Würzburg, Germany.
Department of Biomedical Engineering, Indian Institute of Technology Ropar, India.
Mol Metab. 2024 Dec;90:102044. doi: 10.1016/j.molmet.2024.102044. Epub 2024 Oct 4.
Cancer is a disease characterized by the acquisition of a multitude of unique traits. It has long been understood that cancer cells divert significantly from normal cell metabolism. The most obvious of metabolic changes is that cancer cells strongly rely on glucose conversion by aerobic glycolysis. In addition, they also regularly develop mechanisms to use lipids and fatty acids for their energy needs. Peroxisomes lie central to these adaptive changes of lipid metabolism. Peroxisomes are metabolic organelles that take part in over 50 enzymatic reactions crucial for cellular functioning. Thus, they are essential for an effective and comprehensive use of lipids' energy supplied to cells. Cancer cells display a substantial increase in the biogenesis of peroxisomes and an increased expression of proteins necessary for the enzymatic functions provided by peroxisomes. Moreover, the enzymatic conversion of FAs in peroxisomes is a significant source of reactive oxygen and nitrogen species (ROS/RNS) that strongly impact cancer malignancy. Important regulators in peroxisomal FA oxidation and ROS/RNS generation are the transcription factors of the peroxisome proliferator-activated receptor (PPAR) family. This review describes the metabolic changes in tumorigenesis and cancer progression influenced by peroxisomes. We will highlight the ambivalent role that peroxisomes and PPARs play in the different stages of tumor development and summarize our current understanding of how to capitalize on the comprehension of peroxisomal biology for cancer treatment.
癌症是一种以获得多种独特特征为特征的疾病。长期以来，人们已经认识到癌细胞与正常细胞代谢有很大的不同。最明显的代谢变化是癌细胞强烈依赖有氧糖酵解来转化葡萄糖。此外，它们还经常发展出利用脂质和脂肪酸满足其能量需求的机制。过氧化物酶体在脂质代谢的这些适应性变化中起着核心作用。过氧化物酶体是参与 50 多种对细胞功能至关重要的酶促反应的代谢细胞器。因此，它们对于有效地和全面地利用细胞提供的脂质能量是必不可少的。癌细胞显示出过氧化物酶体生物发生的大量增加，以及参与过氧化物酶体提供的酶促功能所必需的蛋白质的表达增加。此外，过氧化物酶体中 FAs 的酶促转化是活性氧和氮物种 (ROS/RNS) 的重要来源，强烈影响癌症的恶性程度。过氧化物酶体 FA 氧化和 ROS/RNS 生成的重要调节剂是过氧化物酶体增殖物激活受体 (PPAR) 家族的转录因子。这篇综述描述了受过氧化物体影响的肿瘤发生和癌症进展中的代谢变化。我们将强调过氧化物体和 PPAR 在肿瘤发展的不同阶段所扮演的矛盾角色，并总结我们目前对如何利用对过氧化物体生物学的理解来治疗癌症的理解。
