The function and mechanisms of action of lysyl oxidase-like 3 (LOXL3) in cancers

Lysyl oxidase-like 3 (LOXL3) is a key member of the lysyl oxidase (LOX) family and belongs to the copper-dependent amine oxidase family. Its traditional core function is to catalyze the cross-linking of collagen and elastin in the extracellular matrix (ECM), thereby maintaining the structural integrity and normal physiological functions of the ECM. In recent years, studies on cancer molecular mechanisms have confirmed that LOXL3 exhibits abnormal expression in a variety of cancers: in common malignant tumors such as melanoma, liver cancer, gastric cancer, colorectal cancer, and breast cancer, its expression level is significantly higher than that in the corresponding normal tissues. Meanwhile, numerous prognostic analyses have demonstrated that high LOXL3 expression is an independent risk factor for poor prognosis in cancer patients. Such patients usually have shorter progression-free survival (PFS) and overall survival (OS), suggesting that LOXL3 may serve as a potential biomarker for evaluating cancer prognosis. At the functional and mechanistic level, the role of LOXL3 is not limited to ECM remodeling. It can directly affect key biological behaviors of cancer cells, including proliferation, invasion, metastatic potential, and sensitivity to chemotherapeutic drugs, by regulating a variety of intracellular signaling pathways. This article reviews the specific roles and potential molecular mechanisms of LOXL3 in cancer, covering its associations with key cancer pathological processes such as epithelial-mesenchymal transition, maintenance of genomic stability, and regulation of the tumor microenvironment. It focuses on clarifying the specific molecular pathways through which LOXL3 promotes pro-tumor activities in different tumors, as well as the regulatory effects of these pro-tumor activities on patients' relevant prognosis.