ArticleCell reports2020
GDF6-CD99 Signaling Regulates Src and Ewing Sarcoma Growth.
Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Phenotypic Profiling and Activation-Associated Expression of CD99 Ligands on Human Leukocytes.Biology · 2025Article
- CD99: A Key Regulator in Immune Response and Tumor Microenvironment.Biomolecules · 2025Review
- Dual-Faced Role of GDF6 in Cancer: Mechanistic Insights into Its Context-Dependent Regulation of Metastasis and Immune Evasion Across Human Malignancies.Current issues in molecular biology · 2025Article
- Comprehensive analysis of GDFs as therapeutic targets and prognosis biomarkers in gastric cancer.Medicine · 2025Article
- Growth differentiation factor 7 alleviates the proliferation and metastasis of hepatocellular carcinoma.Liver research (Beijing, China) · 2024Article
- Article
- FLT3/CD99 Bispecific Antibody-Based Nanoparticles for Acute Myeloid Leukemia.Cancer research communications · 2024Article
- Sex- and species-specific contribution of CD99 to T cell costimulation during multiple sclerosis.Biology of sex differences · 2024Article
- CD99 Modulates the Proteomic Landscape of Ewing Sarcoma Cells and Related Extracellular Vesicles.International journal of molecular sciences · 2024Article
- Roles of USP1 in Ewing sarcoma.Genes & cancer · 2024Article
- Hypoxia and HIFs in Ewing sarcoma: new perspectives on a multi-facetted relationship.Molecular cancer · 2023Review
- Novel Targeted Therapeutic Strategies for Ewing Sarcoma.Cancers · 2022Review
- Analysis of Transforming Growth Factor ß Family Cleavage Products Secreted Into the Blastocoele of Xenopus laevis Embryos.Journal of visualized experiments : JoVE · 2021Article
- NELL2-cdc42 signaling regulates BAF complexes and Ewing sarcoma cell growth.Cell reports · 2021Article
- EZH2 suppresses endogenous retroviruses and an interferon response in cancers.Genes & cancer · 2021Article
- Clofarabine induces ERK/MSK/CREB activation through inhibiting CD99 on Ewing sarcoma cells.PloS one · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
We report here that the autocrine signaling mediated by growth and differentiation factor 6 (GDF6), a member of the bone morphogenetic protein (BMP) family of cytokines, maintains Ewing sarcoma growth by preventing Src hyperactivation. Surprisingly, Ewing sarcoma depends on the prodomain, not the BMP domain, of GDF6. We demonstrate that the GDF6 prodomain is a ligand for CD99, a transmembrane protein that has been widely used as a marker of Ewing sarcoma. The binding of the GDF6 prodomain to the CD99 extracellular domain results in recruitment of CSK (C-terminal Src kinase) to the YQKKK motif in the intracellular domain of CD99, inhibiting Src activity. GDF6 silencing causes hyperactivation of Src and p21-dependent growth arrest. We demonstrate that two GDF6 prodomain mutants linked to Klippel-Feil syndrome are hyperactive in CD99-Src signaling. These results reveal a cytokine signaling pathway that regulates the CSK-Src axis and cancer cell proliferation and suggest the gain-of-function activity for disease-causing GDF6 mutants.
Indexed as
Identifiers
What OpenQuestion holds
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.