Hijacking the BAF complex: the mechanistic interplay of ARID1A and EWS::FLI1 in Ewing sarcoma

Bibliographic Details
Title: Hijacking the BAF complex: the mechanistic interplay of ARID1A and EWS::FLI1 in Ewing sarcoma
Authors: Erich J. Sohn, David S. Libich
Source: Molecular Oncology, Vol 19, Iss 4, Pp 961-964 (2025)
Publisher Information: Wiley, 2025.
Publication Year: 2025
Collection: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Subject Terms: BAF complex, biomolecular condensate, Ewing sarcoma, EWS::FLI1, prion‐like domain, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1878-0261
1574-7891
Relation: https://doaj.org/toc/1574-7891; https://doaj.org/toc/1878-0261
DOI: 10.1002/1878-0261.13742
Access URL: https://doaj.org/article/53305e4a908d4c85bd955cf9b5650cc4
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  Data: Hijacking the BAF complex: the mechanistic interplay of ARID1A and EWS::FLI1 in Ewing sarcoma
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  Data: <searchLink fieldCode="AR" term="%22Erich+J%2E+Sohn%22">Erich J. Sohn</searchLink><br /><searchLink fieldCode="AR" term="%22David+S%2E+Libich%22">David S. Libich</searchLink>
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  Data: Molecular Oncology, Vol 19, Iss 4, Pp 961-964 (2025)
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  Data: <searchLink fieldCode="DE" term="%22BAF+complex%22">BAF complex</searchLink><br /><searchLink fieldCode="DE" term="%22biomolecular+condensate%22">biomolecular condensate</searchLink><br /><searchLink fieldCode="DE" term="%22Ewing+sarcoma%22">Ewing sarcoma</searchLink><br /><searchLink fieldCode="DE" term="%22EWS%3A%3AFLI1%22">EWS::FLI1</searchLink><br /><searchLink fieldCode="DE" term="%22prion‐like+domain%22">prion‐like domain</searchLink><br /><searchLink fieldCode="DE" term="%22Neoplasms%2E+Tumors%2E+Oncology%2E+Including+cancer+and+carcinogens%22">Neoplasms. Tumors. Oncology. Including cancer and carcinogens</searchLink><br /><searchLink fieldCode="DE" term="%22RC254-282%22">RC254-282</searchLink>
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  Data: 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.
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    Subjects:
      – SubjectFull: BAF complex
        Type: general
      – SubjectFull: biomolecular condensate
        Type: general
      – SubjectFull: Ewing sarcoma
        Type: general
      – SubjectFull: EWS::FLI1
        Type: general
      – SubjectFull: prion‐like domain
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      – SubjectFull: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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      – TitleFull: Hijacking the BAF complex: the mechanistic interplay of ARID1A and EWS::FLI1 in Ewing sarcoma
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