ArticleMolecular oncology2020
Focal adhesion kinase confers pro-migratory and antiapoptotic properties and is a potential therapeutic target in Ewing sarcoma.
Article in Molecular oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- NR4A3 regulates anoikis resistance and metastasis of bladder cancer through EWSR1.Cancer biology & therapy · 2025Article
- The Kinase Inhibitor GNF-7 Is Synthetically Lethal in Topoisomerase 1-Deficient Ewing Sarcoma.Cancers · 2025Article
- Focal adhesion kinase (FAK): emerging target for drug-resistant malignant tumors.Molecular biology reports · 2025Review
- FAK inhibition disrupts tumor growth, apoptosis, and transcriptional regulation in GI-NETs.Endocrine oncology (Bristol, England) · 2025Article
- Integrative analysis of T cell-associated markers in Ewing sarcoma reveals prognostic signatures and immune dynamics.Frontiers in immunology · 2025Article
- MYO6 contributes to tumor progression and enzalutamide resistance in castration-resistant prostate cancer by activating the focal adhesion signaling pathway.Cell communication and signaling : CCS · 2024Article
- Integration of ubiquitination-related genes in predictive signatures for prognosis and immunotherapy response in sarcoma.Frontiers in oncology · 2024Article
- Regulation of Metastasis in Ewing Sarcoma.Cancers · 2022Review
- Article
- New Insights on the Nuclear Functions and Targeting of FAK in Cancer.International journal of molecular sciences · 2022Review
- Targeting the FAK-Src Complex in Desmoplastic Small Round Cell Tumors, Ewing Sarcoma, and Rhabdomyosarcoma.Sarcoma · 2022Article
- EWS-FLI1-targeting peptide identifies Ewing sarcoma tumor boundaries and lymph node metastasis via near-infrared imaging.Molecular oncology · 2021Article
- Focal adhesion kinase inhibitors, a heavy punch to cancer.Discover oncology · 2021Review
- Ewing Sarcoma-Diagnosis, Treatment, Clinical Challenges and Future Perspectives.Journal of clinical medicine · 2021Review
- Sarcoma treatment in the era of molecular medicine.EMBO molecular medicine · 2020Review
- The Role of Tyrosine Kinases as a Critical Prognostic Parameter and Its Targeted Therapies in Ewing Sarcoma.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncogenesis of Ewing sarcoma (EwS), the second most common malignant bone tumor of childhood and adolescence, is dependent on the expression of chimeric EWSR1-ETS fusion oncogenes, most often EWSR1-FLI1 (E/F). E/F expression leads to dysregulation of focal adhesions (FAs) enhancing the migratory capacity of EwS cells. Here, we show that, in EwS cell lines and tissue samples, focal adhesion kinase (FAK) is expressed and phosphorylated at Y397 in an E/F-dependent way involving Ezrin. Employing different EwS cell lines as in vitro models, we found that key malignant properties of E/F are mediated via substrate-independent autophosphorylation of FAK on Y397. This phosphorylation results in enhanced FA formation, Rho-dependent cell migration, and impaired caspase-3-mediated apoptosis in vitro. Conversely, treatment with the FAK inhibitor 15 (1,2,4,5-benzenetetraamine tetrahydrochloride (Y15) enhanced caspase-mediated apoptosis and EwS cell migration, independent from the respective EWSR1-ETS fusion type, mimicking an anoikis-like phenotype and paralleling the effects of FAK siRNA knockdown. Our findings were confirmed in vivo using an avian chorioallantoic membrane model and provide a first rationale for the therapeutic use of FAK inhibitors to impair metastatic dissemination of EwS.
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