Chimeric protein EWS-FLI1 drives cell proliferation in Ewing Sarcoma via overexpression of KCNN1
Chimeric protein EWS-FLI1 drives cell proliferation in Ewing Sarcoma via overexpression of KCNN1
Abstract Ewing sarcoma (ES) is characterized by chimeric fusion proteins, which act as oncogenes. Over the last decade, patient survival has not increased, especially for high risk patients. Knowing that ion channels are studied for their implication in tumorigenesis, the aim of this work is to study the involvement of the SK1 potassium channels in ES. RNA-Seq analyses showed a high restricted expression of KCNN1, the gene encoding SK1, only in ES patients, and its expression is inversely correlated with patient survival. EWS-FLI1 silencing demonstrated the regulation of KCNN1 by these fusion proteins, which bind at GGAA microsatellites near KCNN1 promoter. In addition, KCNN1 has been shown to be involved in the regulation of ES cell proliferation, its silencing being associated with a slowing of the cell cycle. Finally, KCNN1 expression modulates membrane potential and calcium flux suggesting the role of calcium in KCNN1 driving cell proliferation. These results highlight that KCNN1 is a direct EWS-FLI1 and EWS-ERG target, and is involved in the regulation of ES cell proliferation, making it an interesting therapeutic target in ES.
R¨|dini Fran?oise、Dupuy Maryne、Brion R¨|gis、Amiaud J¨|r?me、Chant?me Aur¨|lie、Royer B¨|n¨|dicte Brounais-Le、Georges Steven、Verrecchia Franck、Potier-Cartereau Marie、Regnier Laura、Delattre Olivier、Tesfaye Robel、Vandier Christophe、Lamoureux Fran?ois、Baud?ˉhuin Marc、Mullard Mathilde、Postec Ana?s、Ory Benjamin、Gueguinou Maxime
Nantes Universit¨| Universit¨| d?ˉAngersNantes Universit¨| Universit¨| d?ˉAngersNantes Universit¨| Universit¨| d?ˉAngersNantes Universit¨| Universit¨| d?ˉAngersN2C UMR 1069, University of ToursNantes Universit¨| Universit¨| d?ˉAngersNantes Universit¨| Universit¨| d?ˉAngersNantes Universit¨| Universit¨| d?ˉAngersN2C UMR 1069, University of ToursNantes Universit¨| Universit¨| d?ˉAngersINSERM U830, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Center, Institut CurieNantes Universit¨| Universit¨| d?ˉAngersN2C UMR 1069, University of ToursNantes Universit¨| Universit¨| d?ˉAngersNantes Universit¨| Universit¨| d?ˉAngersNantes Universit¨| Universit¨| d?ˉAngersNantes Universit¨| Universit¨| d?ˉAngersNantes Universit¨| Universit¨| d?ˉAngersN2C UMR 1069, University of Tours
肿瘤学基础医学分子生物学
Calcium / Ewing sarcoma / KCNN1 / Potassium channel / Proliferation
R¨|dini Fran?oise,Dupuy Maryne,Brion R¨|gis,Amiaud J¨|r?me,Chant?me Aur¨|lie,Royer B¨|n¨|dicte Brounais-Le,Georges Steven,Verrecchia Franck,Potier-Cartereau Marie,Regnier Laura,Delattre Olivier,Tesfaye Robel,Vandier Christophe,Lamoureux Fran?ois,Baud?ˉhuin Marc,Mullard Mathilde,Postec Ana?s,Ory Benjamin,Gueguinou Maxime.Chimeric protein EWS-FLI1 drives cell proliferation in Ewing Sarcoma via overexpression of KCNN1[EB/OL].(2025-03-28)[2025-06-04].https://www.biorxiv.org/content/10.1101/2023.04.24.538050.点此复制
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