ArticleBritish journal of cancer2009
Stable interference of EWS-FLI1 in an Ewing sarcoma cell line impairs IGF-1/IGF-1R signalling and reveals TOPK as a new target.
Article in British journal of cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 115 citations in OpenAlex.
- No Identifiable Primary, Only Metastases: Case Report of a Small Round Blue Cell Tumor Consistent With Ewing Sarcoma Presenting With Multisystem Spread in a Young Woman.Clinical medicine insights. Case reports · 2026Article
- The Roles of TOPK in Tumorigenesis and Development: Structure, Mechanisms, Pathways, and Therapeutic Implications.International journal of biological sciences · 2026Review
- YAP1 is a key regulator of EWS::FLI1-dependent malignant transformation upon IGF-1-mediated reprogramming of bone mesenchymal stem cells.Cell reports · 2025Article
- Revisiting 'Hallmarks of Cancer' In Sarcomas.Journal of Cancer · 2024Review
- EHD1-dependent traffic of IGF-1 receptor to the cell surface is essential for Ewing sarcoma tumorigenesis and metastasis.Communications biology · 2023Article
- Investigation of Flavonoid Scaffolds as DAX1 Inhibitors against Ewing Sarcoma through Pharmacoinformatic and Dynamic Simulation Studies.International journal of molecular sciences · 2023Article
- Selective inhibition of HDAC6 regulates expression of the oncogenic driver EWSR1-FLI1 through the EWSR1 promoter in Ewing sarcoma.Oncogene · 2021Article
- The Role of IGF/IGF-IR-Signaling and Extracellular Matrix Effectors in Bone Sarcoma Pathogenesis.Cancers · 2021Review
- Review
- Rationale for Early Detection ofCancers · 2021Review
- Molecular Targets for Novel Therapeutics in Pediatric Fusion-Positive Non-CNS Solid Tumors.Frontiers in pharmacology · 2021Review
- Precision medicine in Ewing sarcoma: a translational point of view.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Review
- An inducible ectopic expression system of EWSR1-FLI1 as a tool for understanding Ewing sarcoma oncogenesis.PloS one · 2020Article
- Slow skeletal muscle troponin T, titin and myosin light chain 3 are candidate prognostic biomarkers for Ewing's sarcoma.Oncology letters · 2019Article
- Intrinsic Disorder of the BAF Complex: Roles in Chromatin Remodeling and Disease Development.International journal of molecular sciences · 2019Article
- Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials.Science translational medicine · 2019Article
- A reciprocal feedback between the PDZ binding kinase and androgen receptor drives prostate cancer.Oncogene · 2019Article
- Tissue engineered models of healthy and malignant human bone marrow.Advanced drug delivery reviews · 2019Review
- Disease-modifying effects of metabolic perturbations in ALS/FTLD.Molecular neurodegeneration · 2018Review
- MicroRNA-216b-3p inhibits lung adenocarcinoma cell growth via regulating PDZ binding kinase/T-LAK-cell-originated protein kinase.Experimental and therapeutic medicine · 2018Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEwing sarcoma is a paradigm of solid tumour -bearing chromosomal translocations resulting in fusion proteins that act as deregulated transcription factors. Ewing sarcoma translocations fuse the EWS gene with an ETS transcription factor, mainly FLI1. Most of the EWS-FLI1 target genes still remain unknown and many have been identified in heterologous model systems.
methodsWe have developed a stable RNA interference model knocking down EWS-FLI1 in the Ewing sarcoma cell line TC71. Gene expression analyses were performed to study the effect of RNA interference on the genetic signature of EWS-FLI1 and to identify genes that could contribute to tumourigenesis.
resultsEWS-FLI1 inhibition induced apoptosis, reduced cell migratory and tumourigenic capacities, and caused reduction in tumour growth. IGF-1 was downregulated and the IGF-1/IGF-1R signalling pathway was impaired. PBK/TOPK (T-LAK cell-originated protein kinase) expression was decreased because of EWS-FLI1 inhibition. We showed that TOPK is a new target gene of EWS-FLI1. TOPK inhibition prompted a decrease in the proliferation rate and a dramatic change in the cell's ability to grow in coalescence.
conclusionThis is the first report of TOPK activity in Ewing sarcoma and suggests a significant role of this MAPKK-like protein kinase in the Ewing sarcoma biology.
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