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靶向SREBP-1介导的脂肪生成作为癌症的潜在治疗策略

Targeting SREBP-1-Mediated Lipogenesis as Potential Strategies for Cancer.

作者信息

Zhao Qiushi, Lin Xingyu, Wang Guan

机构信息

National Engineering Laboratory for AIDS Vaccine, Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun, China.

Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, China.

出版信息

Front Oncol. 2022 Jul 14;12:952371. doi: 10.3389/fonc.2022.952371. eCollection 2022.

Abstract

Sterol regulatory element binding protein-1 (SREBP-1), a transcription factor with a basic helix-loop-helix leucine zipper, has two isoforms, SREBP-1a and SREBP-1c, derived from the same gene for regulating the genes of lipogenesis, including acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase. Importantly, SREBP-1 participates in metabolic reprogramming of various cancers and has been a biomarker for the prognosis or drug efficacy for the patients with cancer. In this review, we first introduced the structure, activation, and key upstream signaling pathway of SREBP-1. Then, the potential targets and molecular mechanisms of SREBP-1-regulated lipogenesis in various types of cancer, such as colorectal, prostate, breast, and hepatocellular cancer, were summarized. We also discussed potential therapies targeting the SREBP-1-regulated pathway by small molecules, natural products, or the extracts of herbs against tumor progression. This review could provide new insights in understanding advanced findings about SREBP-1-mediated lipogenesis in cancer and its potential as a target for cancer therapeutics.

摘要

固醇调节元件结合蛋白-1(SREBP-1)是一种具有碱性螺旋-环-螺旋亮氨酸拉链结构的转录因子,有两种异构体,即SREBP-1a和SREBP-1c,它们来源于同一基因,用于调节脂肪生成相关基因,包括乙酰辅酶A羧化酶、脂肪酸合酶和硬脂酰辅酶A去饱和酶。重要的是,SREBP-1参与多种癌症的代谢重编程,并且一直是癌症患者预后或药物疗效的生物标志物。在本综述中,我们首先介绍了SREBP-1的结构、激活过程及其关键的上游信号通路。然后,总结了SREBP-1在多种类型癌症(如结直肠癌、前列腺癌、乳腺癌和肝细胞癌)中调节脂肪生成的潜在靶点和分子机制。我们还讨论了通过小分子、天然产物或草药提取物靶向SREBP-1调节途径以对抗肿瘤进展的潜在治疗方法。本综述可为理解SREBP-1介导的癌症脂肪生成的最新研究结果及其作为癌症治疗靶点的潜力提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8635/9330218/baecc4b07935/fonc-12-952371-g001.jpg

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