A recent study has shed new light on the biophysical properties of a fusion protein that drives cancer cells, offering potential therapeutic avenues for treating ependymoma, a common childhood brain tumor. Researchers at St. Jude Children’s Research Hospital focused on the abnormal fusion protein ZFTA–RELA, which is implicated in the majority of ependymomas in the brain cortex.
The study revealed that disordered regions within the fusion protein induce the formation of cellular droplets known as condensates. These membraneless organelles play a crucial role in the development of ependymoma. The findings, published in Nature Cell Biology, highlight the importance of understanding how this fusion protein drives the deadly brain tumor.
By dissecting the different regions of the ZFTA–RELA fusion protein, the researchers identified that the ZFTA portion, responsible for DNA binding, is essential for cancer progression. On the other hand, the RELA portion contains a highly disordered region that facilitates condensate formation. These condensates serve as a platform for organizing molecules involved in various cellular processes.
Interestingly, when the disordered region of RELA was removed, condensates failed to form, and ependymoma did not develop in experimental mice. However, when the researchers replaced the RELA portion with other disordered protein regions, the novel fusions still formed condensates, promoting oncogene expression and tumor growth.
The study suggests that condensates present a promising therapeutic target for ependymoma and potentially other cancers driven by fusion proteins. By focusing on the interacting partners within condensates rather than the fusion protein itself, researchers may identify essential targets for disrupting tumor formation.
The researchers believe that their findings could pave the way for new therapeutic interventions for cancers driven by fusion oncoproteins. By unraveling the mechanisms underlying aberrant condensate formation, there is hope for developing targeted therapies that could improve treatment outcomes for patients with these malignancies.
In conclusion, the study provides valuable insights into the role of biomolecular condensates in childhood brain cancer and offers a new perspective on tackling these challenging diseases. Further research in this area may open up novel avenues for precision medicine approaches in cancer therapy.
