ArticleMolecular cancer2019
Exosome-mediated secretion of LOXL4 promotes hepatocellular carcinoma cell invasion and metastasis.
Article in Molecular cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.
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Who cites it
142 citing papers in PubMed, 256 citations in OpenAlex.
- LOXL4: a key regulatory factor at the intersection of fibrosis and tumor progression.Human cell · 2026Review
- Extracellular vesicles in solid tumors: from tumor ecology to engineered therapeutics.Molecular cancer · 2026Review
- Multifaceted Role of Extracellular Vesicles: Intercellular Messengers to Therapeutic Applications: A Narrative Review.Health science reports · 2026Review
- Cell type-resolved analysis identifies LOXL2⁺ fibroblasts as key drivers of malignant stromal remodeling in hepatocellular carcinoma.Discover oncology · 2026Article
- Developing blood extracellular vesicle protein biomarkers for hepatocellular carcinoma: mechanisms, methods, and translation.Journal of nanobiotechnology · 2026Review
- Extracellular matrix stiffness in hepatocellular carcinoma: mechanisms and targeted therapeutic strategies.Frontiers in immunology · 2026Review
- Review
- Pan-cancer analysis of role of LOXL4 and experiment validation in osteosarcoma.Discover oncology · 2025Article
- Predictive effect and clinical diagnosis significance of exosome-related genes for nonalcoholic fatty liver disease-related hepatocellular carcinoma.Scientific reports · 2025Article
- Review
- Identification of mitophagy-related genes in patients with acute myocardial infarction.Hereditas · 2025Article
- Cuproplasia and cuproptosis in hepatocellular carcinoma: mechanisms, relationship and potential role in tumor microenvironment and treatment.Cancer cell international · 2025Review
- [Research progress on the involvement of exosome-mediated intercellular communication in the remodeling and the regulation of invasion and metastasis in the hepatocellular tumor microenvironment].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- ITGA3 promotes pancreatic cancer progression through HIF1α- and c-Myc-driven glycolysis in a collagen I-dependent autocrine manner.Cancer gene therapy · 2025Article
- LOX-induced tubulointerstitial fibrosis via the TGF-β/LOX/Snail axis in diabetic mice.Journal of translational medicine · 2025Article
- Functions and Clinical Applications of Exosomes in Gastric Cancer.International journal of biological sciences · 2025Review
- Vitamin K-dependent gamma-carboxyglutamic acid protein 1 promotes pancreatic ductal adenocarcinoma progression through stabilizing oncoprotein KRAS and tyrosine kinase receptor EGFR.Clinical and translational medicine · 2025Article
- Exosomal crosstalk: the metastatic language of hepatocellular carcinoma.Frontiers in immunology · 2025Review
- The Role of Exosomes in Cancer Progression and Therapy.Biology · 2025Review
- Tumor-derived exosomal miR-1247-3p promotes angiogenesis in bladder cancer by targeting FOXO1.Cancer biology & therapy · 2024Article
82 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLysyl oxidase-like 4 (LOXL4) has been found to be dysregulated in several human malignancies, including hepatocellular carcinoma (HCC). However, the role of LOXL4 in HCC progression remains largely unclear. In this study, we investigated the clinical significance and biological involvement of LOXL4 in the progression of HCC.
methodsLOXL4 expression was measured in HCC tissues and cell lines. Overexpression, shRNA-mediated knockdown, recombinant human LOXL4 (rhLOXL4), and deletion mutants were applied to study the function of LOXL4 in HCC. Exosomes derived from HCC cell lines were assessed for the ability to promote cancer progression in standard assays. The effects of LOXL4 on the FAK/Src pathway were examined by western blotting.
resultsLOXL4 was commonly upregulated in HCC tissues and predicted a poor prognosis. Elevated LOXL4 was associated with tumor differentiation, vascular invasion, and tumor-node-metastasis (TNM) stage. Overexpression of LOXL4 promoted, whereas knockdown of LOXL4 inhibited cell migration and invasion of HCC in vitro, and overexpressed LOXL4 promoted intrahepatic and pulmonary metastases of HCC in vivo. Most interestingly, we found that HCC-derived exosomes transferred LOXL4 between HCC cells, and intracellular but not extracellular LOXL4 promoted cell migration by activating the FAK/Src pathway dependent on its amine oxidase activity through a hydrogen peroxide-mediated mechanism. In addition, HCC-derived exosomes transferred LOXL4 to human umbilical vein endothelial cells (HUVECs) though a paracrine mechanism to promote angiogenesis.
conclusionsTaken together, our data demonstrate a novel function of LOXL4 in tumor metastasis mediated by exosomes through regulation of the FAK/Src pathway and angiogenesis in HCC.
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