The dual role of LOXL4 in the pathogenesis and development of human malignant tumors: a narrative review

Ruai Liu; Bin Li; Jiaji Zi; Ruopeng Zhang; Min Yu; Jinghua Zhou; Yuanqian Pu; Wei Xiong

doi:10.21037/tcr-23-2003

The dual role of LOXL4 in the pathogenesis and development of human malignant tumors: a narrative review

Transl Cancer Res. 2024 Apr 30;13(4):2026-2042. doi: 10.21037/tcr-23-2003. Epub 2024 Apr 17.

Authors

Ruai Liu^{1

2}, Bin Li^{1

2}, Jiaji Zi^{1

2}, Ruopeng Zhang^{1

2}, Min Yu³, Jinghua Zhou^{1

2}, Yuanqian Pu^{1

2}, Wei Xiong^{1

2}

Affiliations

¹ Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dali University, Dali, China.
² Key Laboratory of Clinical Biochemistry Test of Yunnan Province, College of Basic Medical Sciences, Dali University, Dali, China.
³ Laboratory of Biochemistry and Molecular Biology, College of Life Sciences, Yunnan University, Kunming, China.

Abstract

Background and objective: 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.

Methods: 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.

Key content and findings: 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.

Conclusions: 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.

Keywords: Lysyl oxidase-like protein 4 (LOXL4); extracellular matrix (ECM); malignant tumor; tumorigenesis and development.

Publication types

Review