Abnormal Fusion Protein Creates Cell Droplets That May Promote Childhood Brain Tumors
Scientists have uncovered how an abnormal fusion protein causes cell droplet formation, potentially driving childhood brain tumors like ependymoma. This discovery opens new possibilities for targeted therapies in difficult-to-treat cancers.
Recent research has shed light on how an abnormal fusion protein contributes to the development of childhood brain tumors, specifically ependymoma, which is the third most common brain cancer in children. The study focused on the fusion protein ZFTA–RELA, involved in approximately 95% of ependymomas in the brain cortex. Scientists at St. Jude Children's Research Hospital investigated how this fusion protein influences tumor formation.
The researchers discovered that certain disordered regions within the fusion protein lead to the formation of cellular droplets known as condensates. These condensates are akin to 'membraneless organelles' essential for various cellular functions. In ependymoma, these condensates facilitate oncogene expression by concentrating molecules necessary for gene activation.
Experiments demonstrated that when the disordered RELA region of the fusion protein was removed, condensate formation ceased, and tumor development in mice was halted. Interestingly, replacing the RELA region with other disordered protein segments still led to condensate formation and tumor growth, indicating that the formation of these cellular droplets is a critical driver of cancer progression.
The findings highlight condensates as a novel mechanism in oncogenesis, especially in fusion-driven cancers. Targeting the interactions within these condensates could offer new therapeutic strategies, especially since fusion proteins like ZFTA–RELA have proven difficult to target directly. Instead, scientists aim to disrupt the formation or function of these condensates to prevent tumor development.
This groundbreaking study not only advances understanding of how fusion proteins operate but also opens new avenues for treating challenging childhood brain cancers. The research underscores the potential of targeting biomolecular condensates to combat oncogenic processes.
Source: https://medicalxpress.com/news/2025-08-abnormal-fusion-protein-cell-droplets.html
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