ArticleNeoplasia (New York, N.Y.)2019
Lysyl Oxidase-Like Protein 2 Promotes Tumor Lymphangiogenesis and Lymph Node Metastasis in Breast Cancer.
Article in Neoplasia (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
- Extracellular Hsp90α Promotes Tumor Lymphangiogenesis and Lymph Node Metastasis in Breast Cancer.International journal of molecular sciences · 2021Trial
- MEOX1 Coordinates Autocrine-Paracrine Programs via SPHK1/S1P to Promote Lymph Node Metastasis in Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Elevated ERβ expression driven by low ASB8-mediated ubiquitination in lung adenocarcinoma promotes lymph node metastasis via tumor-associated neutrophils.Cell death & disease · 2025Article
- Transient Lymphatic Remodeling Follows Sub-Ablative High-Frequency Irreversible Electroporation Therapy in a 4T1 Murine Model.Annals of biomedical engineering · 2025Article
- Molecular and Cellular Machinery of Lymphatic Metastasis in Breast Cancer.OncoTargets and therapy · 2025Review
- Regulation of VEGFR3 signaling in lymphatic endothelial cells.Frontiers in cell and developmental biology · 2025Review
- A Comprehensive Review of Protein Biomarkers for Invasive Lung Cancer.Current oncology (Toronto, Ont.) · 2024Review
- Pan-cell death-related signature reveals tumor immune microenvironment and optimizes personalized therapy alternations in lung adenocarcinoma.Scientific reports · 2024Article
- The role of LOXL2 in tumor progression, immune response and cellular senescence: a comprehensive analysis.Discover oncology · 2024Article
- Review
- Review
- Lysyl Oxidase (LOX) Family Proteins: Key Players in Breast Cancer Occurrence and Progression.Journal of Cancer · 2024Review
- LOXL2 in Cancer: A Two-Decade Perspective.International journal of molecular sciences · 2023Review
- The aged extracellular matrix and the profibrotic role of senescence-associated secretory phenotype.American journal of physiology. Cell physiology · 2023Review
- Multiple Roles of LOXL2 in the Progression of Hepatocellular Carcinoma and Its Potential for Therapeutic Targeting.International journal of molecular sciences · 2023Review
- AKT-driven epithelial-mesenchymal transition is affected by copper bioavailability in HER2 negative breast cancer cells via a LOXL2-independent mechanism.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- A 3D-Predicted Structure of the Amine Oxidase Domain of Lysyl Oxidase-Like 2.International journal of molecular sciences · 2022Article
- Lysyl Oxidase Family Proteins: Prospective Therapeutic Targets in Cancer.International journal of molecular sciences · 2022Review
- Context Matters: Response Heterogeneity to Collagen-Targeting Approaches in Desmoplastic Cancers.Cancers · 2022Review
- Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor lymphangiogenesis has been previously documented to predict regional lymph node metastasis and promote the spread to distant organs. However, the underlying mechanism initiating tumor lymphangiogenesis remains unclear. Here we described a novel role of tumor cell-derived Lysyl Oxidase-like protein 2 (LOXL2) in promoting lymphangiogenesis and lymph node metastasis in breast cancer. Immunohistochemistry (IHC) analysis of samples from breast cancer patients showed that the expression of LOXL2 was positively correlated with lymphatic vessel density and breast cancer malignancy. In animal studies, LOXL2-overexpressing breast cancer cells significantly increased lymphangiogenesis and lymph node metastasis, whereas knockdown of LOXL2 suppressed both processes. In order to study the mechanisms of lymphangiogenesis progression, we performed further in vitro investigations and the data revealed that LOXL2 significantly enhanced lymphatic endothelial cells (LECs) invasion and tube formation through directly activation of the Akt-Snail and Erk pathways. Moreover, LOXL2 also stimulated fibroblasts to secrete high level of pro- lymphangiogenic factors VEGF-C and SDF-1α. Taken together, our study elucidates a novel function of tumor cell secreted LOXL2 in lymphangiogenesis and lymph node metastasis, demonstrating that LOXL2 serves as a promising target for anti-lymphangiogenesis and anti-metastasis therapies for breast cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.