Liu Ruai, Li Bin, Zi Jiaji, Zhang Ruopeng, Yu Min, Zhou Jinghua, Pu Yuanqian, Xiong Wei
Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dali University, Dali, China.
Key Laboratory of Clinical Biochemistry Test of Yunnan Province, College of Basic Medical Sciences, Dali University, Dali, China.
Transl Cancer Res. 2024 Apr 30;13(4):2026-2042. doi: 10.21037/tcr-23-2003. Epub 2024 Apr 17.
Lysyl oxidase-like protein 4 (LOXL4) is a secreted copper-dependent amine oxidase involved in the assembly and maintenance of extracellular matrix (ECM), playing a critical role in ECM formation and repair. Tumor-stroma interactions and ECM dysregulation are closely associated with the mechanisms underlying tumor initiation and progression. LOXL4 is the latest identified member of the lysyl oxidase (LOX) protein family. Currently, there is limited and controversial research on the role of LOXL4 in human malignancies. Its specific regulatory pathways, mechanisms, and roles in the occurrence, development, and treatment of malignancies remain incompletely understood. This article aims to illustrate the primary protein structure and the function of LOXL4 protein, and the relationship between LOXL4 protein and the occurrence and development of human malignant tumors to provide a reference for further clinical research.
We searched the English literature on LOXL4 in the occurrence and development of various malignant tumors in PubMed and Web of Science. The search keywords include "cancer" "LOXL4" "malignant tumor" "tumorigenesis and development", etc.
LOXL4 is up-regulated in human gastric cancer, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, esophageal carcinoma and colorectal cancer, but down-regulated in human bladder cancer and lung cancer and inhibits tumor growth. There are two conflicting reports of both upregulation and downregulation in hepatocellular carcinoma, suggesting that LOXL4 has a bidirectional effect of promoting or inhibiting cancer in different types of human malignant tumors. We further explore the application prospect of LOXL4 protein in the study of malignant tumors, laying a theoretical foundation for the clinical diagnosis, treatment and screening of prognostic markers of malignant tumors.
LOXL4 exerts a bidirectional regulatory role, either inhibiting or promoting tumors depending on the type of cancer. We still need more research to further confirm the molecular mechanism of LOXL4 in cancer progression.
赖氨酰氧化酶样蛋白4（LOXL4）是一种分泌型铜依赖性胺氧化酶，参与细胞外基质（ECM）的组装和维持，在ECM形成和修复中起关键作用。肿瘤-基质相互作用和ECM失调与肿瘤发生和进展的机制密切相关。LOXL4是赖氨酰氧化酶（LOX）蛋白家族最新鉴定的成员。目前，关于LOXL4在人类恶性肿瘤中的作用的研究有限且存在争议。其在恶性肿瘤发生、发展和治疗中的具体调控途径、机制及作用仍不完全清楚。本文旨在阐述LOXL4蛋白的一级结构和功能，以及LOXL4蛋白与人类恶性肿瘤发生发展的关系，为进一步的临床研究提供参考。
我们在PubMed和Web of Science中搜索了关于LOXL4在各种恶性肿瘤发生发展中的英文文献。搜索关键词包括“癌症”“LOXL4”“恶性肿瘤”“肿瘤发生与发展”等。
LOXL4在人类胃癌、乳腺癌、卵巢癌、头颈部鳞状细胞癌、食管癌和结直肠癌中上调，但在人类膀胱癌和肺癌中下调并抑制肿瘤生长。在肝细胞癌中，有两份相互矛盾的报告分别显示其上调和下调，这表明LOXL4在不同类型的人类恶性肿瘤中具有促进或抑制癌症的双向作用。我们进一步探讨了LOXL4蛋白在恶性肿瘤研究中的应用前景，为恶性肿瘤的临床诊断、治疗及预后标志物筛选奠定理论基础。
LOXL4发挥双向调节作用，根据癌症类型的不同，既可以抑制肿瘤，也可以促进肿瘤。我们仍需要更多研究来进一步证实LOXL4在癌症进展中的分子机制。
