ArticleOncotarget2016
CD99 triggering induces methuosis of Ewing sarcoma cells through IGF-1R/RAS/Rac1 signaling.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Metabolic cell death in cancer: mechanisms and therapeutic potential.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- Article
- Development of an Anti-CD99 Antibody Enables Targeting of Diffuse Midline Glioma.Cancer research · 2025Article
- Article
- CD99: A Key Regulator in Immune Response and Tumor Microenvironment.Biomolecules · 2025Review
- Potential Role of CD99 Signaling Pathway in Schwann Cell Dysfunction in Diabetic Foot Ulcers Based on Single-Cell Transcriptome Analysis.Journal of diabetes research · 2025Article
- Review
- Cellular Regulation of Macropinocytosis.International journal of molecular sciences · 2024Review
- Extracellular Interactors of the IGF System: Impact on Cancer Hallmarks and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Transcriptome Analysis Reveals the Induction of Apoptosis-Related Genes by a Monoclonal Antibody against a New Epitope of CD99 on T-Acute Lymphoblastic Leukemia.Antibodies (Basel, Switzerland) · 2024Article
- Article
- Anti-CD99 Antibody Therapy Triggers Macrophage-Dependent Ewing Cell Death In Vitro and Myeloid Cell Recruitment In Vivo.Antibodies (Basel, Switzerland) · 2024Article
- Engagement of CD99 Activates Distinct Programs in Ewing Sarcoma and Macrophages.Cancer immunology research · 2024Article
- Resistance Improvement and Sensitivity Enhancement of Cancer Therapy by a Novel Antitumor Candidate onto A2780 CP and A2780 S Cell Lines.Reports of biochemistry & molecular biology · 2023Article
- Design, synthesis and biological evaluation of Nucleosidic CD99 inhibitors that selectively reduce Ewing sarcoma viability.European journal of medicinal chemistry · 2023Article
- Anti-c-MET Fab-Grb2-Gab1 Fusion Protein-Mediated Interference of c-MET Signaling Pathway Induces Methuosis in Tumor Cells.International journal of molecular sciences · 2022Article
- The autophagy inducer trehalose stimulates macropinocytosis in NF1-deficient glioblastoma cells.Cancer cell international · 2022Article
- Methuosis Contributes to Jaspine-B-Induced Cell Death.International journal of molecular sciences · 2022Article
- Novel Targeted Therapeutic Strategies for Ewing Sarcoma.Cancers · 2022Review
- miR-214-3p Is Commonly Downregulated by EWS-FLI1 and by CD99 and Its Restoration Limits Ewing Sarcoma Aggressiveness.Cancers · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
CD99 is a cell surface molecule that has emerged as a novel target for Ewing sarcoma (EWS), an aggressive pediatric bone cancer. This report provides the first evidence of methuosis in EWS, a non-apoptotic form of cell death induced by an antibody directed against the CD99 molecule. Upon mAb triggering, CD99 induces an IGF-1R/RAS/Rac1 complex, which is internalized into RAB5-positive endocytic vacuoles. This complex is then dissociated, with the IGF-1R recycling to the cell membrane while CD99 and RAS/Rac1 are sorted into immature LAMP-1-positive vacuoles, whose excessive accumulation provokes methuosis. This process, which is not detected in CD99-expressing normal mesenchymal cells, is inhibited by disruption of the IGF-1R signaling, whereas enhanced by IGF-1 stimulation. Induction of IGF-1R/RAS/Rac1 was also observed in the EWS xenografts that respond to anti-CD99 mAb, further supporting the role of the IGF/RAS/Rac1 axis in the hyperstimulation of macropinocytosis and selective death of EWS cells. Thus, we describe a vulnerability of EWS cells, including those resistant to standard chemotherapy, to a treatment with anti-CD99 mAb, which requires IGF-1R/RAS signaling but bypasses the need for their direct targeting. Overall, we propose CD99 targeting as new opportunity to treat EWS patients resistant to canonical apoptosis-inducing agents.
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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.