ETS Proteins Bind with Glucocorticoid Receptors: Relevance for Treatment of Ewing Sarcoma

Swati Srivastava, Nishanth Belugali Nataraj, Arunachalam Sekar, Soma Ghosh, Chamutal Bornstein, Diana Drago-Garcia, Lee Roth, Donatella Romaniello, Ilaria Marrocco, Eyal David, Yuval Gilad, Mattia Lauriola, Ron Rotkopf, Adi Kimchi, Yuya Haga, Yasuo Tsutsumi, Olivier Mirabeau, Didier Surdez, Andrei Zinovyev, Olivier DelattreHeinrich Kovar, Ido Amit, Yosef Yarden

Risultato della ricerca: Contributo in rivistaArticolo in rivista


The glucocorticoid receptor (GR) acts as a ubiquitous cortisol-dependent transcription factor (TF). To identify co-factors, we used protein-fragment complementation assays and found that GR recognizes FLI1 and additional ETS family proteins, TFs relaying proliferation and/or migration signals. Following steroid-dependent translocation of FLI1 and GR to the nucleus, the FLI1-specific domain (FLS) binds with GR and strongly enhances GR's transcriptional activity. This interaction has functional consequences in Ewing sarcoma (ES), childhood and adolescence bone malignancies driven by fusions between EWSR1 and FLI1. In vitro, GR knockdown inhibited the migration and proliferation of ES cells, and in animal models, antagonizing GR (or lowering cortisol) retarded both tumor growth and metastasis from bone to lung. Taken together, our findings offer mechanistic rationale for repurposing GR-targeting drugs for the treatment of patients with ES.
Lingua originaleEnglish
pagine (da-a)104-117
Numero di pagine14
RivistaCell Reports
Stato di pubblicazionePubblicato - 2019


  • Ewing sarcoma
  • cancer therapy
  • glucocorticoid receptor
  • metastasis
  • protein-fragment complementation assay


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