Hijacking the BAF complex: the mechanistic interplay of ARID1A and EWS::FLI1 in Ewing sarcoma
Ewing sarcoma, an aggressive pediatric cancer, is driven by the EWS::FLI1 fusion protein, which disrupts gene expression by hijacking the BAF chromatin remodeling complex. Central to this mechanism is the formation of biomolecular condensates, mediated by the prion‐like domains (PrLDs) of EWS and AR...
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| Format: | Article |
| Language: | English |
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Wiley
2025-04-01
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| Series: | Molecular Oncology |
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| Online Access: | https://doi.org/10.1002/1878-0261.13742 |
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| author | Erich J. Sohn David S. Libich |
| author_facet | Erich J. Sohn David S. Libich |
| author_sort | Erich J. Sohn |
| collection | DOAJ |
| description | Ewing sarcoma, an aggressive pediatric cancer, is driven by the EWS::FLI1 fusion protein, which disrupts gene expression by hijacking the BAF chromatin remodeling complex. Central to this mechanism is the formation of biomolecular condensates, mediated by the prion‐like domains (PrLDs) of EWS and ARID1A, a core BAF subunit. ARID1A serves as a critical interface between EWS::FLI1 and the BAF complex, with its condensate‐forming ability essential for the aberrant gene expression that drives tumor growth. The loss of condensate‐competent ARID1A significantly impairs tumor progression, identifying it as a potential therapeutic target. However, targeting condensate formation is challenging due to the transient nature of the interactions involved, complicating the development of effective inhibitors. This work underscores the importance of further investigation into therapeutic strategies aimed at disrupting condensate formation in Ewing sarcoma and other related malignancies. |
| format | Article |
| id | doaj-art-53305e4a908d4c85bd955cf9b5650cc4 |
| institution | OA Journals |
| issn | 1574-7891 1878-0261 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj-art-53305e4a908d4c85bd955cf9b5650cc42025-08-20T02:08:57ZengWileyMolecular Oncology1574-78911878-02612025-04-0119496196410.1002/1878-0261.13742Hijacking the BAF complex: the mechanistic interplay of ARID1A and EWS::FLI1 in Ewing sarcomaErich J. Sohn0David S. Libich1Greehey Children's Cancer Research Institute and Department of Biochemistry and Structural Biology The University of Texas Health Science Center at San Antonio San Antonio TX USAGreehey Children's Cancer Research Institute and Department of Biochemistry and Structural Biology The University of Texas Health Science Center at San Antonio San Antonio TX USAEwing sarcoma, an aggressive pediatric cancer, is driven by the EWS::FLI1 fusion protein, which disrupts gene expression by hijacking the BAF chromatin remodeling complex. Central to this mechanism is the formation of biomolecular condensates, mediated by the prion‐like domains (PrLDs) of EWS and ARID1A, a core BAF subunit. ARID1A serves as a critical interface between EWS::FLI1 and the BAF complex, with its condensate‐forming ability essential for the aberrant gene expression that drives tumor growth. The loss of condensate‐competent ARID1A significantly impairs tumor progression, identifying it as a potential therapeutic target. However, targeting condensate formation is challenging due to the transient nature of the interactions involved, complicating the development of effective inhibitors. This work underscores the importance of further investigation into therapeutic strategies aimed at disrupting condensate formation in Ewing sarcoma and other related malignancies.https://doi.org/10.1002/1878-0261.13742BAF complexbiomolecular condensateEwing sarcomaEWS::FLI1prion‐like domain |
| spellingShingle | Erich J. Sohn David S. Libich Hijacking the BAF complex: the mechanistic interplay of ARID1A and EWS::FLI1 in Ewing sarcoma Molecular Oncology BAF complex biomolecular condensate Ewing sarcoma EWS::FLI1 prion‐like domain |
| title | Hijacking the BAF complex: the mechanistic interplay of ARID1A and EWS::FLI1 in Ewing sarcoma |
| title_full | Hijacking the BAF complex: the mechanistic interplay of ARID1A and EWS::FLI1 in Ewing sarcoma |
| title_fullStr | Hijacking the BAF complex: the mechanistic interplay of ARID1A and EWS::FLI1 in Ewing sarcoma |
| title_full_unstemmed | Hijacking the BAF complex: the mechanistic interplay of ARID1A and EWS::FLI1 in Ewing sarcoma |
| title_short | Hijacking the BAF complex: the mechanistic interplay of ARID1A and EWS::FLI1 in Ewing sarcoma |
| title_sort | hijacking the baf complex the mechanistic interplay of arid1a and ews fli1 in ewing sarcoma |
| topic | BAF complex biomolecular condensate Ewing sarcoma EWS::FLI1 prion‐like domain |
| url | https://doi.org/10.1002/1878-0261.13742 |
| work_keys_str_mv | AT erichjsohn hijackingthebafcomplexthemechanisticinterplayofarid1aandewsfli1inewingsarcoma AT davidslibich hijackingthebafcomplexthemechanisticinterplayofarid1aandewsfli1inewingsarcoma |