Department of Internal Medicine, Università degli Studi di Genova, Viale Benedetto XV, 6, 16132, Genova, Italy.
Department of Internal Medicine, Università degli Studi di Genova, Viale Benedetto XV, 6, 16132, Genova, Italy; Sidra Medicine, Al Gharrafa St, Ar-Rayyan, Qatar.
Cancer Lett. 2020 Nov 28;493:19-30. doi: 10.1016/j.canlet.2020.07.010. Epub 2020 Jul 22.
Sterol synthesis is a highly complex and integrated pathway in mammals. In the present review, we briefly summarize the main steps of this pathway, especially concerning its main rate-limiting enzymes, HMG-CoA reductase (HMGCR) and squalene epoxidase (SQLE), in relation with cancer. We focus on studies reporting key findings linking cholesterol with cancer. The inhibition of HMGCR and SQLE to prevent and inhibit cancer are reviewed. Finally, a pan-cancer review of publicly available data on genomic aberrations in the main enzymes involved in sterol biosynthesis and their transcription factors is reported, providing hitherto unexplored findings that may be the subject of future research in cancer metabolomics and tumor targeted treatment.
甾醇合成是哺乳动物中一个高度复杂和综合的途径。在本综述中,我们简要总结了该途径的主要步骤,特别是与癌症相关的关键限速酶 HMG-CoA 还原酶 (HMGCR) 和鲨烯环氧化酶 (SQLE)。我们重点介绍了报告胆固醇与癌症之间关键联系的研究。我们还回顾了抑制 HMGCR 和 SQLE 以预防和抑制癌症的研究。最后,我们对涉及甾醇生物合成的主要酶及其转录因子的基因组异常的公开可用数据进行了泛癌症综述,提供了迄今为止尚未探索的发现,这些发现可能成为癌症代谢组学和肿瘤靶向治疗未来研究的主题。