ArticleJCI insight2020
Wnt/β-catenin-activated Ewing sarcoma cells promote the angiogenic switch.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- SARC028 Samples Reveal an Interplay between TGF-β, IFN Signaling, and Low HLA Class I Expression as Contributors to Ewing Sarcoma Checkpoint Blockade Resistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Autocrine TGFβ2 enforces a transcriptionally hybrid cell state in Ewing sarcoma.Science advances · 2026Article
- Choosing the right animal model for sarcoma research.Cellular and molecular life sciences : CMLS · 2026Review
- A Vascularized Microphysiological System Reproducing Endochondral Ossification in Vitro to Study Ewing Sarcoma Proliferation and Migration.Advanced functional materials · 2026Article
- Stromal Steroid 5 Alpha-Reductase 2 Promotes Prostate Growth through WNT5A-Lymphoid Enhancer-Binding Factor 1-Insulin-Like Growth Factor 1 Signaling in Benign Prostatic Hyperplasia.The American journal of pathology · 2025Article
- Article
- From 2D to 3D: transforming malignant bone tumor research with advanced culture models.Journal of Zhejiang University. Science. B · 2025Review
- Unveiling Let-7a's Therapeutic Role in Ewing Sarcoma Through Molecular Docking and Deformation Energy Analysis.Current issues in molecular biology · 2025Article
- New Approaches to Investigate Novel Agents in Ewing Sarcoma: A Report From the Children's Oncology Group Bone Tumor Committee.Pediatric blood & cancer · 2025Review
- TGFβ Inhibition during Radiotherapy Enhances Immune Cell Infiltration and Decreases Metastases in Ewing Sarcoma.Cancer research communications · 2025Article
- Single-Cell Analysis Clarifies Pathological Heterogeneity in Tenosynovial Giant Cell Tumor and Identifies Biomarkers for Predicting Disease Recurrence.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Autocrine TGFβ2 enforces a transcriptionally hybrid cell state in Ewing sarcoma.bioRxiv : the preprint server for biology · 2025Article
- Targeting mesothelin-CD24 axis repolarizes tumor-associated macrophages to potentiate PD-1 blockade therapy in high-grade serous ovarian cancer.Journal for immunotherapy of cancer · 2025Article
- Article
- Wnt signaling aberrant activation drives ameloblastoma invasion and recurrence: bioinformatics and in vitro insights.BMC oral health · 2024Article
- Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy.Journal of hematology & oncology · 2024Review
- Pediatric Solid Cancers: Dissecting the Tumor Microenvironment to Improve the Results of Clinical Immunotherapy.International journal of molecular sciences · 2024Review
- Cadherin-11 contributes to the heterogenous and dynamic Wnt-Wnt-β-catenin pathway activation in Ewing sarcoma.PloS one · 2024Article
- Cancer-Associated Fibroblast-Like Tumor Cells Remodel the Ewing Sarcoma Tumor Microenvironment.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Recruitment of transcription factor ETS1 to activated accessible regions promotes the transcriptional program of cilia genes.Nucleic acids research · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Wnt/β-catenin signaling is active in small subpopulations of Ewing sarcoma cells, and these cells display a more metastatic phenotype, in part due to antagonism of EWS-FLI1-dependent transcriptional activity. Importantly, these β-catenin-activated Ewing sarcoma cells also alter secretion of extracellular matrix (ECM) proteins. We thus hypothesized that, in addition to cell-autonomous mechanisms, Wnt/β-catenin-active tumor cells might contribute to disease progression by altering the tumor microenvironment (TME). Analysis of transcriptomic data from primary patient biopsies and from β-catenin-active versus -nonactive tumor cells identified angiogenic switch genes as being highly and reproducibly upregulated in the context of β-catenin activation. In addition, in silico and in vitro analyses, along with chorioallantoic membrane assays, demonstrated that β-catenin-activated Ewing cells secreted factors that promote angiogenesis. In particular, activation of canonical Wnt signaling leads Ewing sarcoma cells to upregulate expression and secretion of proangiogenic ECM proteins, collectively termed the angiomatrix. Significantly, our data show that induction of the angiomatrix by Wnt-responsive tumor cells is indirect and is mediated by TGF-β. Mechanistically, Wnt/β-catenin signaling antagonizes EWS-FLI1-dependent repression of TGF-β receptor type 2, thereby sensitizing tumor cells to TGF-β ligands. Together, these findings suggest that Wnt/β-catenin-active tumor cells can contribute to Ewing sarcoma progression by promoting angiogenesis in the local TME.
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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.