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赖氨酰氧化酶(LOX)家族蛋白:乳腺癌发生和进展中的关键因子

Lysyl Oxidase (LOX) Family Proteins: Key Players in Breast Cancer Occurrence and Progression.

作者信息

Li Jinsong, Wang Xinmeng, Liu Ruai, Zi Jiaji, Li Yihan, Li Zhengliang, Xiong Wei

机构信息

Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dali University, Dali 671000, Yunnan, China.

Key Laboratory of Clinical Biochemistry Testing in Universities of Yunnan Province, College of Basic Medical Sciences, Dali University, Dali 671000, Yunnan, China.

出版信息

J Cancer. 2024 Aug 13;15(16):5230-5243. doi: 10.7150/jca.98688. eCollection 2024.

Abstract

The lysyl oxidase (LOX) family proteins are secreted copper-dependent amine oxidases, comprised of five paralogues: LOX and LOX-like 1-4 (LOXL1-4), which are characterized by catalytic activity contributing to the remodeling of the cross-linking of the structural extracellular matrix (ECM). ECM remodeling plays a key role in the angiogenesis surrounding tumours, whereby a corrupt tumour microenvironment (TME) takes shape. Additionally, dysregulation and aberrant expression of LOX family proteins have been implicated in the occurrence and progression of various types of human cancers, including lung cancer, hepatocellular carcinoma, gastric cancer, renal cell carcinoma, and colorectal cancer. Breast cancer is the most prevalent malignant tumour in women worldwide, and its incidence rate is increasing annually. In recent years, a growing body of evidence has revealed significant upregulation of LOX family proteins in breast cancer, which contributes to cancer cell proliferation, invasion, and metastasis. Furthermore, elevated expression of LOX family proteins is closely associated with poor prognosis in breast cancer patients. We herein review the structure, regulation, function, and mechanisms of LOX family proteins in the occurrence and progression of breast cancer. In addition, we highlight recent insights into their mechanisms and their potential involvement in the clinical value and novel biological roles of LOX family members in tumour progression and the TME of breast cancer. This review will provide a theoretical basis and reference for clinical diagnosis and treatment of breast cancer, as well as for the screening of effective LOX-specific inhibitors.

摘要

赖氨酰氧化酶(LOX)家族蛋白是分泌型铜依赖性胺氧化酶,由五个旁系同源物组成:LOX和LOX样蛋白1-4(LOXL1-4),其特征在于催化活性有助于结构细胞外基质(ECM)交联的重塑。ECM重塑在肿瘤周围的血管生成中起关键作用,由此形成腐败的肿瘤微环境(TME)。此外,LOX家族蛋白的失调和异常表达与包括肺癌、肝细胞癌、胃癌、肾细胞癌和结直肠癌在内的各种类型人类癌症的发生和进展有关。乳腺癌是全球女性中最常见的恶性肿瘤,其发病率逐年上升。近年来,越来越多的证据表明乳腺癌中LOX家族蛋白显著上调,这有助于癌细胞增殖、侵袭和转移。此外,LOX家族蛋白的高表达与乳腺癌患者的不良预后密切相关。我们在此综述了LOX家族蛋白在乳腺癌发生和进展中的结构、调控、功能及机制。此外,我们强调了对其机制的最新见解,以及它们在乳腺癌进展和TME中可能参与的临床价值和新生物学作用。本综述将为乳腺癌的临床诊断和治疗以及有效LOX特异性抑制剂的筛选提供理论依据和参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fc3/11375560/2153f52e636a/jcav15p5230g001.jpg

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