Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, C/ Sant Quintí 77, 08041 Barcelona Spain; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, C/ Antoni M. Claret 167, 08025 Barcelona, Spain.
Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, C/ Sant Quintí 77, 08041 Barcelona Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), C/ Monforte de Lemos 3-5, 28029 Madrid, Spain.
Semin Cancer Biol. 2021 Aug;73:134-157. doi: 10.1016/j.semcancer.2020.11.012. Epub 2020 Nov 26.
Cholesterol is essential for a variety of functions in endocrine-related cells, including hormone and steroid production. We have reviewed the progress to date in research on the role of the main cholesterol-containing lipoproteins; low-density lipoprotein (LDL) and high-density lipoprotein (HDL), and their impact on intracellular cholesterol homeostasis and carcinogenic pathways in endocrine-related cancers. Neither LDL-cholesterol (LDL-C) nor HDL-cholesterol (HDL-C) was consistently associated with endocrine-related cancer risk. However, preclinical studies showed that LDL receptor plays a critical role in endocrine-related tumor cells, mainly by enhancing circulating LDL-C uptake and modulating tumorigenic signaling pathways. Although scavenger receptor type BI-mediated uptake of HDL could enhance cell proliferation in breast, prostate, and ovarian cancer, these effects may be counteracted by the antioxidant and anti-inflammatory properties of HDL. Moreover, 27-hydroxycholesterol a metabolite of cholesterol promotes tumorigenic processes in breast and epithelial thyroid cancer. Furthermore, statins have been reported to reduce the incidence of breast, prostate, pancreatic, and ovarian cancer in large clinical trials, in part because of their ability to lower cholesterol synthesis. Overall, cholesterol homeostasis deregulation in endocrine-related cancers offers new therapeutic opportunities, but more mechanistic studies are needed to translate the preclinical findings into clinical therapies.
胆固醇对于内分泌相关细胞的多种功能至关重要，包括激素和类固醇的产生。我们回顾了目前关于主要含胆固醇脂蛋白；低密度脂蛋白（LDL）和高密度脂蛋白（HDL）的作用及其对细胞内胆固醇稳态和内分泌相关癌症致癌途径的研究进展。低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）均与内分泌相关癌症风险无一致性关联。然而，临床前研究表明，LDL 受体在内分泌相关肿瘤细胞中发挥关键作用，主要通过增强循环 LDL-C 的摄取并调节致癌信号通路。虽然清道夫受体 B1 介导的 HDL 摄取可增强乳腺癌、前列腺癌和卵巢癌细胞的增殖，但这些作用可能被 HDL 的抗氧化和抗炎特性抵消。此外，胆固醇的代谢产物 27-羟胆固醇可促进乳腺癌和甲状腺上皮癌的肿瘤发生过程。此外，他汀类药物在大型临床试验中已被报道可降低乳腺癌、前列腺癌、胰腺癌和卵巢癌的发病率，部分原因是其降低胆固醇合成的能力。总之，内分泌相关癌症中胆固醇稳态失调提供了新的治疗机会，但需要更多的机制研究将临床前发现转化为临床治疗。
