ArticleCell death & disease2022
TrkC, a novel prognostic marker, induces and maintains cell survival and metastatic dissemination of Ewing sarcoma by inhibiting EWSR1-FLI1 degradation.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
- Delayed growth of SK-ES-1 Ewing sarcoma tumor xenografts is associated with reduced Trk and IGF1R pathway markers.Oncotarget · 2026Article
- Review
- Modelling EWS::FLI1 protein fluctuations reveal determinants of tumor plasticity in Ewing sarcoma.EMBO molecular medicine · 2026Article
- A practical approach to better identify NTRK 1-3 fusion-positive mesenchymal neoplasms by pan-Trk immunohistochemistry.Virchows Archiv : an international journal of pathology · 2025Article
- Role of TRKC and NT-3 proteins in the progression and prognosis of colorectal cancer.Translational cancer research · 2025Article
- TrkC protects against osteoarthritis progression by maintaining articular cartilage homeostasis.International journal of biological sciences · 2025Article
- Modifications in the C-terminal tail of TrkC significantly alter neurotrophin-3-promoted outgrowth of neurite-like processes from PC12 cells.Biochemistry and biophysics reports · 2024Article
- Unlocking epigenetics for precision treatment of Ewing's sarcoma.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Primary Ewing's sarcoma of the uterine cervix: a case report and review of the literature.Journal of cancer research and clinical oncology · 2024Review
- Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Upregulation of EWSR1-FLI1 expression has been associated with invasiveness, induced cell survival, metastatic dissemination, and acquisition of self-renewal traits in Ewing sarcoma (ES). Although existing evidence implies that TrkC expression is linked to the pathogenesis of other cancer types, its role and the mechanism behind its correlation with EWSR1-FLI1 in the pathogenesis of ES remain unclear. In this study, we uncovered a novel physiological role of TrkC as a key regulator of EWSR1-FLI1 involved in the survival and metastatic dissemination of ES. TrkC was observed to be frequently overexpressed in human metastatic ES cells in vitro and in vivo, facilitating enhanced survival, tumorigenicity, and metastasis of ES cells. TrkC-mediated metastasis of ES cells was induced by the inhibition of the proteasomal degradation of EWSR1-FLI1 via the TrkC/EWSR1-FLI1 complex, which subsequently enabled the induction of the target proteins, EGR2 and NKX2.2. Moreover, TrkC significantly inhibited tumor suppressor activity of TGF-β through reduction of the mRNA expression of one of its receptors, TGFBR2 via TrkC-induced stabilization of EWSR1-FLI1. Furthermore, loss of TrkC expression inhibited tumor growth and metastasis in experimental mouse models. This study is the first to report the involvement and functional role of TrkC in the pathogenesis of ES, suggesting important implications for understanding the alterations of TrkC in Ewing tumors.
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