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• W3041559678 abstract "Abstract Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood characterized by the inability to exit the proliferative myoblast-like stage. The alveolar fusion positive subtype (FP-ARMS) is the most aggressive and is mainly caused by the expression of PAX3/7-FOXO1 oncoproteins, which are challenging pharmacological targets. Thus, other therapeutic vulnerabilities resulting from gene expression changes are progressively being recognized. Here, we identified the DEAD box RNA helicase 5 (DDX5) as a potential therapeutic target to inhibit FP-ARMS growth. We show that DDX5 is overexpressed in alveolar RMS cells, demonstrating that its depletion drastically decreases FP-ARMS viability and slows tumor growth in xenograft models. Mechanistically, we provide evidence that DDX5 functions upstream the G9a/AKT survival signalling pathway, by modulating G9a protein stability. Finally, we show that G9a interacts with PAX3-FOXO1 and regulates its activity, thus sustaining FP-ARMS myoblastic state. Together, our findings identify a novel survival-promoting loop in FP-ARMS and highlight DDX5 as potential therapeutic target to arrest rhabdomyosarcoma growth." @default.
• W3041559678 created "2020-07-16" @default.
• W3041559678 creator A5011375543 @default.
• W3041559678 creator A5018125068 @default.
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• W3041559678 date "2020-07-10" @default.
• W3041559678 modified "2023-09-23" @default.
• W3041559678 title "The RNA helicase DDX5 promotes alveolar rhabdomyosarcoma growth and survival" @default.
• W3041559678 cites W2018363492 @default.
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• W3041559678 doi "https://doi.org/10.1101/2020.07.08.194092" @default.
• W3041559678 hasPublicationYear "2020" @default.
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