赖氨酰氧化酶家族在肝细胞癌发生发展中的作用

覃小宾; 李祖隆; 曾胜澜; 谭利婷; 乐滢玉; 毛德文

doi:10.3969/j.issn.1001-5256.2022.03.039

赖氨酰氧化酶家族在肝细胞癌发生发展中的作用

DOI: 10.3969/j.issn.1001-5256.2022.03.039

1.
广西中医药大学研究生院，南宁 530021
2.
广西中医药大学第一附属医院肝病科，南宁 530023

基金项目:

国家自然科学基金 (81960841);

国家自然科学基金面上项目 (82060848);

广西自然科学基金课题 (2018GXNSFAA281096);

广西中医药大学校级一般硕士研究生创新项目 (YCXJ2021039)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：毛德文、乐滢玉负责研究选题；曾胜澜、谭利婷参与收集数据，设计论文框架；覃小宾、李祖隆负责修订论文；毛德文、覃小宾负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
毛德文，mdwboshi2005@163.com

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出版历程
- 收稿日期: 2021-07-29
- 录用日期: 2021-10-11
- 出版日期: 2022-03-20

Role of lysyl oxidase family in the development and progression of hepatocellular carcinoma

1.
Graduate School of Guangxi University of Chinese medicine, Nanning 530021, China
2.
Department of Hepatology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China

Research funding:

Research funding: National Natural Science Foundation of China (81960841);

General Project of National Natural Science Foundation of China (82060848);

Natural Science Foundation of Guangxi Province (2018GXNSFAA281096);

Innovation Project of General Postgraduates in Guangxi University of Traditional Chinese Medicine (YCXJ2021039)

More Information

Corresponding author: MAO Dewen, mdwboshi2005@163.com(ORCID: 0000-0001-9438-9325)

摘要

摘要: 赖氨酰氧化酶(LOX)家族是由LOX和LOX样蛋白(LOXL1~4)组成的铜胺氧化酶，在肿瘤组织中过表达，通过细胞外基质的共价交联促进肿瘤转移，具有细胞生长控制、肿瘤抑制、衰老和趋化作用。近年来，越来越多的证据表明LOX家族成员在肝细胞癌(HCC)的发病机理中发挥着关键作用，提示它们作为治疗靶点的巨大潜力。本文就LOX家族成员在HCC发生发展中的作用及中药提取物通过调节LOX家族对HCC的干预作用进行综述，以期为防治HCC的深入研究提供参考。
- 癌, 肝细胞 /
- 蛋白赖氨酸6-氧化酶 /
- 中草药
Abstract: Lysyl oxidase (LOX) family is a group of copper-containing amine oxidases composed of LOX and LOX-like proteins (LOXL1, LOXL2, LOXL3, and LOXL4). It is overexpressed in tumor tissue and promotes tumor metastasis through covalent cross-linking of extracellular matrix, with the functions of cell growth control, tumor inhibition, senescence, and chemotaxis. In recent years, more and more evidence has shown that LOX family members play a key role in the pathogenesis of hepatocellular carcinoma (HCC), suggesting that they have great potential as therapeutic targets. This article reviews the role of LOX family members in the development and progression of HCC and the intervention effect of traditional Chinese medicine extracts on HCC by regulating LOX family, in order to provide a reference for further research on the prevention and treatment of HCC.
- Carcinoma, Hepatocellular /
- Protein-Lysine 6-Oxidase /
- Drugs, Chinese Herbal

HTML全文

图 1 LOX家族成员Swiss-model三维结构模型^[8-12]

下载: 全尺寸图片幻灯片

图 2 黄芩素干预HCC的作用示意图

下载: 全尺寸图片幻灯片

图 3 白藜芦醇干预HCC的作用示意图

下载: 全尺寸图片幻灯片

图 4 红景天苷干预HCC的作用示意图

下载: 全尺寸图片幻灯片

图 5 肉苁蓉苯乙醇苷干预HCC的作用示意图

下载: 全尺寸图片幻灯片

表 1 LOX家族成员在HCC中的促进作用

作用	成员	机制	参考文献
促进血管生成	LOX	通过p38MAPK信号上调VEGF；	[13]
		通过整合素αV/β5/Akt-核Sp1通路上调VEGFR2	[15-16]
	LOXL1	增强FAK血管内皮细胞内的MAPK信号通路	[17]
	LOXL2	通过Snail信号上调VEGF；沉积Ⅳ型胶原，协调血管基底膜的支架	[18-19]
	LOXL4	经外泌体的介导转移到亲代HCC细胞和内皮细胞上，促进血管生成	[20]
促进EMT	LOX	在HIF-1α介导下降低E-钙黏蛋白，增加波形蛋白、Slug蛋白以及TWIST蛋白	[23]
促进EMT	LOXL2	以Snail依赖方式降低E-钙黏蛋白；与E-钙黏蛋白启动子结合，激活FAK/Src信号	[24-25]
重塑肿瘤微环境	LOX	诱导Ⅳ型胶原线性重排，重塑ECM使机械应力增加	[29]
	LOXL2	活化成纤维细胞，调节细胞骨架重组，募集骨髓来源细胞归巢到转移部位；增强M2巨噬细胞的极化，导致免疫抑制	[30-32]
	LOXL4	激活PD-L1的表达，诱导巨噬细胞免疫抑制；	^[33]
		激活FAK/Src通路，增强ECM硬度；	^[20]
		通过Smad依赖和JunB/Fra2途径参与血管基质重塑	^[34]

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