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脂肪酸去饱和酶2在人类癌症中的多方面调控及功能

Multifaceted regulation and functions of fatty acid desaturase 2 in human cancers.

作者信息

Li Yan-Ling, Tian Hao, Jiang Jun, Zhang Yi, Qi Xiao-Wei

机构信息

Department of Breast and Thyroid Surgery, Southwest Hospital, Third Military Medical University Chongqing 400038, China.

出版信息

Am J Cancer Res. 2020 Dec 1;10(12):4098-4111. eCollection 2020.

Abstract

As an important hallmark of metabolic reprogramming in cancer, a disruption in fatty acid metabolism contributes to tumor proliferation, cell migration and invasion, and other tumor cell behaviors. In recent years, more and more studies have been conducted on fatty acid desaturase 2 (FADS2), the first rate-limiting enzyme for the biosynthesis of polyunsaturated fatty acids. These studies have found that FADS2 is abnormally expressed in cancers of the breast, lung, liver, and esophagus; melanoma; leukemia; and other malignant tumors. Furthermore, its expression is significantly correlated with tumor proliferation, cell migration and invasion, clonal formation, angiogenesis, ferroptosis, resistance to radiotherapy, histological grade, metastasis to lymph nodes, clinical stage, and prognosis. The abnormal expression of FADS2 results in an imbalance of cell membrane phospholipids, which disrupts the fluidity of the membrane structure and the transmission of signals and promotes the production of proinflammatory factors and arachidonic acid (AA) metabolites, ultimately harming human health. This article aims to systematically review the structural characteristics of FADS2; its function, expression, and mechanism of action; and the factors affecting its activity. This review also provides new ideas and strategies for the development of treatments aimed at the metabolic reprogramming of tumors.

摘要

作为癌症代谢重编程的一个重要标志,脂肪酸代谢紊乱有助于肿瘤增殖、细胞迁移和侵袭以及其他肿瘤细胞行为。近年来,针对多不饱和脂肪酸生物合成的首个限速酶——脂肪酸去饱和酶2(FADS2)开展了越来越多的研究。这些研究发现,FADS2在乳腺癌、肺癌、肝癌、食管癌、黑色素瘤、白血病及其他恶性肿瘤中异常表达。此外,其表达与肿瘤增殖、细胞迁移和侵袭、克隆形成、血管生成、铁死亡、放疗抗性、组织学分级、淋巴结转移、临床分期及预后显著相关。FADS2的异常表达导致细胞膜磷脂失衡,破坏膜结构的流动性和信号传递,并促进促炎因子和花生四烯酸(AA)代谢产物的产生,最终损害人类健康。本文旨在系统综述FADS2的结构特征、其功能、表达及作用机制以及影响其活性的因素。本综述还为针对肿瘤代谢重编程的治疗方法开发提供新思路和策略。

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