ArticleCancer research2008
EWS-FLI1 suppresses NOTCH-activated p53 in Ewing's sarcoma.
Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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
60 citing papers in PubMed, 111 citations in OpenAlex.
- Unveiling Let-7a's Therapeutic Role in Ewing Sarcoma Through Molecular Docking and Deformation Energy Analysis.Current issues in molecular biology · 2025Article
- Upregulated NOTCH2 Expression Is Implicated in the Clinical Aggressiveness of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma.International journal of dermatology · 2025Article
- Renal ewing sarcoma in a young female: a case report and review of targeted therapy.Frontiers in surgery · 2025Article
- Pharmacological targeting of P300/CBP reveals EWS::FLI1-mediated senescence evasion in Ewing sarcoma.Molecular cancer · 2024Article
- Article
- Rethinking growth factors: the case of BMP9 during vessel maturation.Vascular biology (Bristol, England) · 2022Review
- Single-cell RNA profiling identifies diverse cellular responses to EWSR1/FLI1 downregulation in Ewing sarcoma cells.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Review
- Ewing Sarcoma-Diagnosis, Treatment, Clinical Challenges and Future Perspectives.Journal of clinical medicine · 2021Review
- YAP/TAZ inhibition reduces metastatic potential of Ewing sarcoma cells.Oncogenesis · 2021Article
- DLX5 promotes osteosarcoma progression via activation of the NOTCH signaling pathway.American journal of cancer research · 2021Article
- Precision medicine for human cancers with Notch signaling dysregulation (Review).International journal of molecular medicine · 2020Review
- Mutant p53 antagonizes p63/p73-mediated tumor suppression via Notch1.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- TP53 in bone and soft tissue sarcomas.Pharmacology & therapeutics · 2019Review
- EWS-FLI1 low Ewing sarcoma cells demonstrate decreased susceptibility to T-cell-mediated tumor cell apoptosis.Oncotarget · 2019Article
- Cytogenetic characterization of the malignant primitive neuroectodermal SK-PN-DW tumor cell line.BMC cancer · 2019Article
- MicroRNA‑34b promotes proliferation, migration and invasion of Ewing's sarcoma cells by downregulating Notch1.Molecular medicine reports · 2018Article
- Article
- EWS-FLI1 perturbs MRTFB/YAP-1/TEAD target gene regulation inhibiting cytoskeletal autoregulatory feedback in Ewing sarcoma.Oncogene · 2017Article
- The endochondral bone protein CHM1 sustains an undifferentiated, invasive phenotype, promoting lung metastasis in Ewing sarcoma.Molecular oncology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Although p53 is the most frequently mutated gene in cancer, half of human tumors retain wild-type p53, whereby it is unknown whether normal p53 function is compromised by other cancer-associated alterations. One example is Ewing's sarcoma family tumors (ESFT), where 90% express wild-type p53. ESFT are characterized by EWS-FLI1 oncogene fusions. Studying 6 ESFT cell lines, silencing of EWS-FLI1 in a wild-type p53 context resulted in increased p53 and p21(WAF1/CIP1) levels, causing cell cycle arrest. Using a candidate gene approach, HEY1 was linked to p53 induction. HEY1 was rarely expressed in 59 primary tumors, but consistently induced upon EWS-FLI1 knockdown in ESFT cell lines. The NOTCH signaling pathway targets HEY1, and we show NOTCH2 and NOTCH3 to be expressed in ESFT primary tumors and cell lines. Upon EWS-FLI1 silencing, NOTCH3 processing accompanied by nuclear translocation of the activated intracellular domain was observed in all but one p53-mutant cell line. In cell lines with the highest HEY1 induction, NOTCH3 activation was the consequence of JAG1 transcriptional induction. JAG1 modulation by specific siRNA, NOTCH-processing inhibition by either GSI or ectopic NUMB1, and siRNA-mediated HEY1 knockdown all inhibited p53 and p21(WAF1/CIP1) induction. Conversely, forced expression of JAG1, activated NOTCH3, or HEY1 induced p53 and p21(WAF1/CIP1). These results indicate that suppression of EWS-FLI1 reactivates NOTCH signaling in ESFT cells, resulting in p53-dependent cell cycle arrest. Our data link EWS-FLI1 to the NOTCH and p53 pathways and provide a plausible basis both for NOTCH tumor suppressor effects and oncogenesis of cancers that retain wild-type p53.
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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.