The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA.
Antioxid Redox Signal. 2023 Jul;39(1-3):102-140. doi: 10.1089/ars.2023.0340.
Cholesterol is a type of lipid that plays a crucial role in building and maintaining cell membranes, producing certain hormones, and aiding in digestion. The two main types of cholesterol are low-density lipoprotein and high-density lipoprotein, and maintaining a healthy balance between them is essential for cellular function and organism health. Cholesterol metabolism is a complex and dynamic process that involves biosynthesis, uptake, efflux, transport, and esterification. Disruptions in cholesterol metabolism are implicated in all stages of cancer, contributing to drug resistance, immune evasion, and autophagy dysfunction. These disruptions have also been linked to various types of regulated cell death, such as apoptosis, anoikis, lysosome-dependent cell death, pyroptosis, NETosis, necroptosis, entosis, ferroptosis, alkaliptosis, immunogenic cell death, and paraptosis. Understanding the complex interplay between cholesterol metabolism and cell death and their impact on cancer development and progression is still a significant challenge. In addition, there is currently a lack of reliable biomarkers that can accurately reflect cholesterol metabolism dysregulation in cancer. To develop more specific and effective cholesterol metabolism-targeted therapies, a better understanding of the mechanisms by which cholesterol metabolism dysregulation contributes to cell death and cancer progression is needed. In addition, improving the accuracy and reliability of biomarkers will be crucial for monitoring and diagnosing cholesterol-related cancer subtypes and evaluating the effectiveness of cholesterol metabolism-targeted therapies. These efforts will require ongoing research and collaboration among multidisciplinary teams of scientists and clinicians. 39, 102-140.
胆固醇是一种脂质,在构建和维持细胞膜、产生某些激素以及促进消化方面发挥着至关重要的作用。胆固醇有两种主要类型,即低密度脂蛋白和高密度脂蛋白,维持它们之间的健康平衡对于细胞功能和机体健康至关重要。胆固醇代谢是一个复杂而动态的过程,涉及生物合成、摄取、外排、转运和酯化。胆固醇代谢的紊乱与癌症的各个阶段都有关联,导致药物耐药性、免疫逃逸和自噬功能障碍。这些紊乱还与各种类型的受调控细胞死亡有关,如细胞凋亡、失巢凋亡、溶酶体依赖性细胞死亡、细胞焦亡、NETosis、坏死性凋亡、侵入、铁死亡、碱细胞死亡、免疫原性细胞死亡和 Paraptosis。理解胆固醇代谢与细胞死亡之间的复杂相互作用及其对癌症发展和进展的影响仍然是一个重大挑战。此外,目前缺乏能够准确反映癌症中胆固醇代谢失调的可靠生物标志物。为了开发更特异和有效的胆固醇代谢靶向治疗方法,需要更好地理解胆固醇代谢失调如何导致细胞死亡和癌症进展的机制。此外,提高生物标志物的准确性和可靠性对于监测和诊断与胆固醇相关的癌症亚型以及评估胆固醇代谢靶向治疗方法的有效性至关重要。这些努力将需要多学科科学家和临床医生团队的持续研究和合作。