Li Yunkuo, Wu Shouwang, Zhao Xiaodong, Hao Shiming, Li Faping, Wang Yuxiong, Liu Bin, Zhang Difei, Wang Yishu, Zhou Honglan
Department of Urology, The First Hospital of Jilin University, Changchun, China.
Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China.
Front Pharmacol. 2023 Mar 8;14:1130747. doi: 10.3389/fphar.2023.1130747. eCollection 2023.
Lipid metabolism reprogramming is an important hallmark of tumor progression. Cancer cells require high levels of lipid synthesis and uptake not only to support their continued replication, invasion, metastasis, and survival but also to participate in the formation of biological membranes and signaling molecules. Sterol regulatory element binding proteins (SREBPs) are core transcription factors that control lipid metabolism and the expression of important genes for lipid synthesis and uptake. A growing number of studies have shown that SREBPs are significantly upregulated in human cancers and serve as intermediaries providing a mechanistic link between lipid metabolism reprogramming and malignancy. Different subcellular localizations, including endoplasmic reticulum, Golgi, and nucleus, play an indispensable role in regulating the cleavage maturation and activity of SREBPs. In this review, we focus on the relationship between aberrant regulation of SREBPs activity in three organelles and tumor progression. Because blocking the regulation of lipid synthesis by SREBPs has gradually become an important part of tumor therapy, this review also summarizes and analyzes several current mainstream strategies.
脂质代谢重编程是肿瘤进展的一个重要标志。癌细胞不仅需要高水平的脂质合成和摄取来支持其持续的复制、侵袭、转移和存活,还需要参与生物膜和信号分子的形成。固醇调节元件结合蛋白(SREBPs)是控制脂质代谢以及脂质合成和摄取相关重要基因表达的核心转录因子。越来越多的研究表明,SREBPs在人类癌症中显著上调,并作为脂质代谢重编程与恶性肿瘤之间机制联系的中介。包括内质网、高尔基体和细胞核在内的不同亚细胞定位在调节SREBPs的切割成熟和活性方面发挥着不可或缺的作用。在本综述中,我们重点关注三种细胞器中SREBPs活性的异常调节与肿瘤进展之间的关系。由于阻断SREBPs对脂质合成的调节已逐渐成为肿瘤治疗的重要组成部分,本综述还总结并分析了几种当前的主流策略。