ArticleCell research2020
Wnt signaling and Loxl2 promote aggressive osteosarcoma.
Article in Cell research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 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 and longitudinal transcriptomics-guided engineering of FZD1-targeting precision nanotherapy against osteosarcoma cancer stem cells.Bioactive materials · 2026Article
- ZMAT1 Promotes Osteoclastogenesis Through TRIM46 Mediated YAP1 Degradation and Inhibits Osteoblastogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A conceptual blueprint for "turning cold to hot" in Osteosarcoma: from TME stratification hypotheses to adaptive therapeutic prospects.Cell communication and signaling : CCS · 2026Review
- Targeting Wnt3a and Loxl2 Synergistically Induces Ferroptosis in Liver Cancer Stem Cells and Suppresses Tumorigenesis.Cancer science · 2026Article
- The extracellular matrix in inflammation and cancer.Molecular biomedicine · 2026Review
- METTL3-mediated mMolecular cancer · 2026Article
- FGF-23 facilitates osteosarcoma metastasis by modulating the miR-4463/LOXL2 axis expression via the ERK, p38, and JNK signaling pathway.International journal of medical sciences · 2026Article
- Musculoskeletal disorders: does cuproptosis hold the key?Frontiers in cell and developmental biology · 2026Review
- Research advances in the role of osteoblasts and their derivatives in the development, recurrence, and distant metastasis of malignant bone tumors: a narrative review.EFORT open reviews · 2025Review
- HMGB1 and Its Signaling Pathway in Osteosarcoma: Current Advances in Targeted Therapy.Current issues in molecular biology · 2025Review
- LncSNHGs: new targets in osteosarcoma.Cancer gene therapy · 2025Review
- Exploring the Tumor Microenvironment in Osteosarcoma: Driver of Resistance and Progression.Cancers · 2025Review
- High Expression of miR-218-5p in the Peripheral Blood Stream and Tumor Tissues of Pediatric Patients with Sarcomas.Biochemical genetics · 2025Article
- TRIM47 Facilitates Osteosarcoma Progression via Destabilising FBP1 and Thus Activation of Wnt/β-Catenin Pathway.Journal of cellular and molecular medicine · 2025Article
- Identification of Nogo-B as a potential therapeutic target of osteosarcoma via stereochemically selective covalent probes.Cell death & disease · 2025Article
- Exosomal Gene Biomarkers in Osteosarcoma: Mifepristone as a Targeted Therapeutic Revealed by Multi-Omics Analysis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Overexpression of FOS enhances the malignant potential of eutopic endometrial stromal cells in patients with endometriosis‑associated ovarian cancer.Oncology reports · 2025Article
- Exosomes derived from FN14-overexpressing BMSCs activate the NF-κB signaling pathway to induce PANoptosis in osteosarcoma.Apoptosis : an international journal on programmed cell death · 2025Article
- Role of long noncoding RNAs in the regulation of epithelial‑mesenchymal transition in osteosarcoma (Review).Oncology reports · 2025Review
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma (OS) is the most frequent primary malignant bone tumor in urgent need of better therapies. Using genetically modified mouse models (GEMMs), we demonstrate that Wnt signaling promotes c-Fos-induced OS formation via the actions of the collagen-modifying enzyme Loxl2. c-Fos/AP-1 directly regulates the expression of the Wnt ligands Wnt7b and Wnt9a in OS cells through promoter binding, and Wnt7b and Wnt9a in turn promote Loxl2 expression in murine and human OS cells through the transcription factors Zeb1 and Zeb2. Concordantly, inhibition of Wnt ligand secretion by inactivating the Wnt-less (Wls) gene in osteoblasts in c-Fos GEMMs either early or in a therapeutic setting reduces Loxl2 expression and progression of OS. Wls-deficient osteosarcomas proliferate less, are less mineralized and are enriched in fibroblastic cells surrounded by collagen fibers. Importantly, Loxl2 inhibition using either the pan-Lox inhibitor BAPN or a specific inducible shRNA reduces OS cell proliferation in vitro and decreases tumor growth and lung colonization in murine and human orthotopic OS transplantation models. Finally, OS development is delayed in c-Fos GEMMs treated with BAPN or with specific Loxl2 blocking antibodies. Congruently, a strong correlation between c-FOS, LOXL2 and WNT7B/WNT9A expression is observed in human OS samples, and c-FOS/LOXL2 co-expression correlates with OS aggressiveness and decreased patient survival. Therefore, therapeutic targeting of Wnt and/or Loxl2 should be considered to potentiate the inadequate current treatments for pediatric, recurrent, and metastatic OS.
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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.