Wang Xinmeng, Wang Xiaoyi, Li Yihan, Zhao Dan, He Jintao, Wang Lin, Li Zhengliang, Xiong Wei
Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dali University, Dali, Yunnan, China.
Key Laboratory of Clinical Biochemistry Testing in Universities of Yunnan Province, College of Basic Medical Sciences, Dali University, Dali, Yunnan, China.
PeerJ. 2025 Aug 7;13:e19628. doi: 10.7717/peerj.19628. eCollection 2025.
Cancer is one of the primary causes of human mortality and a significant barrier to increasing human life expectancy. The effective screening, early diagnosis, and treatment of cancer have long been clinical challenges, and thus new biomarkers or molecular targets must be identified to improve the diagnosis and treatment of cancer patients. Lysyl oxidase like 1 (LOXL1), a secreted copper-dependent amine oxidase, is commonly expressed in a variety of cell types. LOXL1 can maintain the steady state of elastin, engage in extracellular matrix (ECM) remodelling. LOXL1 has diverse biological functions, and its dysregulation is the basis of many clinical diseases. The abnormal expression or activation of LOXL1 can disrupt the cellular microenvironment, contributing to the development of various diseases, such as atherosclerosis, tissue damage, fibrosis, and cancer. Recent research has revealed that LOXL1 is often overexpressed in a majority of cancers, where it plays a role in regulating tumor growth and metastasis. However, some studies have also suggested that LOXL1 may have a tumor-suppressive function. Research has indicated that the LOXL1 protein is reduced in human renal cell carcinoma (RCC) and bladder cancer (BLCA), where it acts to suppress tumor growth. Conversely, it is upregulated in human salivary adenoid cystic carcinoma (SACC), non-small cell lung cancer (NSCLC), pleural mesothelioma (PM), brain glioma, prostate cancer (PRAD), gastric cancer (GC), breast cancer (BC), thyroid carcinoma (THCA), pancreatic adenocarcinoma (PAAD), and osteosarcoma (OS). The expression of LOXL1 in colorectal cancer (CRC) remains a topic of debate, as it may either be upregulated or downregulated. These findings imply that LOXL1 may have a dual role in cancer, either inhibiting or facilitating carcinogenesis. This article provides a comprehensive review of the structure and function of LOXL1, along with its associations with cancer. Additionally, it explores the role of LOXL1 in tumor microenvironment remodeling, tumorigenesis, metastasis, and the molecular mechanisms that underpin these processes.
癌症是人类死亡的主要原因之一,也是延长人类预期寿命的重大障碍。癌症的有效筛查、早期诊断和治疗长期以来一直是临床面临的挑战,因此必须识别出新的生物标志物或分子靶点,以改善癌症患者的诊断和治疗。赖氨酰氧化酶样1(LOXL1)是一种分泌型铜依赖性胺氧化酶,在多种细胞类型中普遍表达。LOXL1可以维持弹性蛋白的稳态,参与细胞外基质(ECM)重塑。LOXL1具有多种生物学功能,其失调是许多临床疾病的基础。LOXL1的异常表达或激活会破坏细胞微环境,导致各种疾病的发生,如动脉粥样硬化、组织损伤、纤维化和癌症。最近的研究表明,LOXL1在大多数癌症中经常过度表达,在调节肿瘤生长和转移中发挥作用。然而,一些研究也表明,LOXL1可能具有肿瘤抑制功能。研究表明,LOXL1蛋白在人类肾细胞癌(RCC)和膀胱癌(BLCA)中减少,在这些癌症中它起到抑制肿瘤生长的作用。相反,它在人类涎腺腺样囊性癌(SACC)、非小细胞肺癌(NSCLC)、胸膜间皮瘤(PM)、脑胶质瘤、前列腺癌(PRAD)、胃癌(GC)、乳腺癌(BC)、甲状腺癌(THCA)、胰腺腺癌(PAAD)和骨肉瘤(OS)中上调。LOXL1在结直肠癌(CRC)中的表达仍然是一个有争议的话题,因为它可能上调或下调。这些发现意味着LOXL1在癌症中可能具有双重作用,要么抑制要么促进致癌作用。本文全面综述了LOXL1的结构和功能,以及它与癌症的关联。此外,还探讨了LOXL1在肿瘤微环境重塑、肿瘤发生、转移以及支撑这些过程的分子机制中的作用。