Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China.
Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Int J Mol Sci. 2024 Mar 30;25(7):3874. doi: 10.3390/ijms25073874.
Squalene epoxidase (SQLE) is a key enzyme in the mevalonate-cholesterol pathway that plays a critical role in cellular physiological processes. It converts squalene to 2,3-epoxysqualene and catalyzes the first oxygenation step in the pathway. Recently, intensive efforts have been made to extend the current knowledge of SQLE in cancers through functional and mechanistic studies. However, the underlying mechanisms and the role of SQLE in cancers have not been fully elucidated yet. In this review, we retrospected current knowledge of SQLE as a rate-limiting enzyme in the mevalonate-cholesterol pathway, while shedding light on its potential as a diagnostic and prognostic marker, and revealed its therapeutic values in cancers. We showed that SQLE is regulated at different levels and is involved in the crosstalk with iron-dependent cell death. Particularly, we systemically reviewed the research findings on the role of SQLE in different cancers. Finally, we discussed the therapeutic implications of SQLE inhibitors and summarized their potential clinical values. Overall, this review discussed the multifaceted mechanisms that involve SQLE to present a vivid panorama of SQLE in cancers.
鲨烯环氧酶（SQLE）是甲羟戊酸-胆固醇途径中的一种关键酶，在细胞生理过程中起着至关重要的作用。它将鲨烯转化为 2,3-环氧鲨烯，并催化途径中的第一个氧化步骤。最近，通过功能和机制研究，人们已经做出了巨大的努力来扩展 SQLE 在癌症中的现有知识。然而，其在癌症中的潜在作用和机制尚未得到充分阐明。在这篇综述中，我们回顾了 SQLE 作为甲羟戊酸-胆固醇途径中的限速酶的现有知识，同时阐明了它作为诊断和预后标志物的潜力，并揭示了它在癌症中的治疗价值。我们表明，SQLE 在不同水平上受到调节，并参与与铁依赖性细胞死亡的串扰。特别地，我们系统地综述了 SQLE 在不同癌症中的作用的研究结果。最后，我们讨论了 SQLE 抑制剂的治疗意义，并总结了它们的潜在临床价值。总的来说，这篇综述讨论了涉及 SQLE 的多种机制，呈现了 SQLE 在癌症中的生动全景。
