ArticleOncology reports2020
LOXL2 upregulates hypoxia‑inducible factor‑1α signaling through Snail‑FBP1 axis in hepatocellular carcinoma cells.
Article in Oncology reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- The prediction value of LOXL-2 in the clinical pathology and prognosis of cancers: A meta-analysis and bioinformatics analysis.Scientific reports · 2025Pooled it
- Single-cell profiling reveals a novel CAF subpopulation linking stromal heterogeneity to immune suppression in breast cancer subtypes.Journal of translational medicine · 2026Article
- Metabolic Regulation of Immune Responses: Molecular Mechanisms, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Cell type-resolved analysis identifies LOXL2⁺ fibroblasts as key drivers of malignant stromal remodeling in hepatocellular carcinoma.Discover oncology · 2026Article
- The role of fructose-1,6-bisphosphatase 1 on regulating the cancer progression and drug resistance.Discover oncology · 2025Review
- Angiogenesis and Immunosuppressive Niche in Hepatocellular Carcinoma: Reshaping Vascular - Immune Axis to Potentiate antiPD - 1/PD - L1 Therapy.Cancer management and research · 2025Review
- LOXL2 inhibition ameliorates pulmonary artery remodeling in pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- A Comprehensive Review of Protein Biomarkers for Invasive Lung Cancer.Current oncology (Toronto, Ont.) · 2024Review
- Protein regulator of cytokinesis 1 accentuates cholangiocarcinoma progression via mTORC1-mediated glycolysis.Human cell · 2024Article
- Sorafenib inhibits ossification of the posterior longitudinal ligament by blocking LOXL2-mediated vascularization.Bone research · 2024Article
- Mechanisms of angiogenesis in tumour.Frontiers in oncology · 2024Review
- The lactate metabolism and protein lactylation in epilepsy.Frontiers in cellular neuroscience · 2024Review
- Lysyl oxidase-like 2 promotes stemness and enhances antitumor effects of gefitinib in head and neck cancer via IFIT1 and IFIT3.Cancer science · 2023Article
- LOXL2 in Cancer: A Two-Decade Perspective.International journal of molecular sciences · 2023Review
- Multiple Roles of LOXL2 in the Progression of Hepatocellular Carcinoma and Its Potential for Therapeutic Targeting.International journal of molecular sciences · 2023Review
- Hypoxia Alters the Proteome Profile and Enhances the Angiogenic Potential of Dental Pulp Stem Cell-Derived Exosomes.Biomolecules · 2022Article
- MiR-29a Curbs Hepatocellular Carcinoma Incidence via Targeting ofInternational journal of molecular sciences · 2022Article
- Article
- Ubiquinone Metabolism and Transcription HIF-1 Targets Pathway Are Toxicity Signature Pathways Present in Extracellular Vesicles of Paraquat-Exposed Human Brain Microvascular Endothelial Cells.International journal of molecular sciences · 2021Article
- Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments.Molecular cancer · 2021Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lysyl oxidase‑like 2 (LOXL2), a member of the lysyl oxidase gene family, is involved in the progression of hepatocellular carcinoma progression and metastasis. Increased expression of LOXL2 has been identified in several types of cancer, including hepatocellular carcinoma. Recently, LOXL2 has been reported to promote epithelial‑mesenchymal transition by reducing E‑cadherin expression via the upregulation of Snail expression. The present study provided evidence demonstrating that LOXL2 inhibited the expression of fructose‑1, 6‑biphosphatase (FBP1) and enhanced the glycolysis of Huh7 and Hep3B hepatocellular carcinoma cell lines in a Snail‑dependent manner. Overexpression of the point‑mutated form of LOXL2 [LOXL2(Y689F)], which lacks enzymatic activity, does not affect the expression of Snail1 or FBP1. Notably, targeting extracellular LOXL2 of Huh7 cells with a therapeutic antibody was unable to abolish its regulation on the expression of Snail and FBP1. Knockdown of LOXL2 also interrupted the angiogenesis of Huh7 and Hep3B cells, and this effect could be rescued by the overexpression of Snail. Furthermore, upregulation of hypoxia‑inducible factor 1α (HIF‑1α) and vascular endothelial growth factor (VEGF) expression was observed in Huh7 and Hep3B cells expressing wild‑type LOXL2. Notably, the selective LOXL2 inhibitor LOXL2‑IN‑1 could upregulate the expression of FBP1 and inhibit the expression of Snail, HIF‑1α and VEGF in HCC cells, but not in FBP1‑knockdown cells. The results of the present study indicated that the intracellular activity of LOXL2 upregulated HIF‑1α/VEGF signaling pathways via the Snail‑FBP1 axis, and this phenomenon could be inhibited by LOXL2 inhibition. Collectively, these findings further support that LOXL2 exhibits an important role in the progression of hepatocellular carcinoma and implicates LOXL2 as a potential therapeutic agent for the treatment of this disease.
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