Molecular Oncology: Hijacking the BAF complex: the mechanistic interplay of ARID1A and EWS::FLI1 in Ewing sarcoma (Libich Lab)
Erich J. Sohn, David S. Libich
Abstract
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.
Since 2004, UT Health San Antonio, Greehey Children’s Cancer Research Institute’s (Greehey CCRI) mission has been to advance scientific knowledge relevant to childhood cancer, contribute to understanding its causes, and accelerate the translation of knowledge into novel therapies. Greehey CCRI strives to have a national and global impact on childhood cancer by discovering, developing, and disseminating new scientific knowledge. Our mission consists of three key areas — research, clinical, and education.
Stay connected with the Greehey CCRI on Facebook, Twitter, LinkedIn, and Instagram.