論文

査読有り 国際誌
2019年10月1日

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

Cell reports
  • 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 Delattre
  • ,
  • Heinrich Kovar
  • ,
  • Ido Amit
  • ,
  • Yosef Yarden

29
1
開始ページ
104
終了ページ
117
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.celrep.2019.08.088

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.

リンク情報
DOI
https://doi.org/10.1016/j.celrep.2019.08.088
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31577941
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899513
ID情報
  • DOI : 10.1016/j.celrep.2019.08.088
  • PubMed ID : 31577941
  • PubMed Central 記事ID : PMC6899513

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