A recent investigation has highlighted a vital enzyme that plays a role in the formation of selenoproteins, paving the way for innovative approaches to treat specific cancers in children.
A recent study from the University of Würzburg unveiled a key enzyme involved in producing selenoproteins, opening new strategies for treating certain types of cancer in children.
Selenoproteins are essential for various biological functions, such as breaking down toxic substances, aiding the immune response, and controlling metabolic processes. Nonetheless, in certain situations, these proteins can be exploited, allowing cancer cells to evade death. Glutathione peroxidase 4 (GPX4) is one such protein that plays a crucial role in helping cells resist damage and allowing cancer cells to survive.
“The protective function of GPX4 presents a considerable obstacle for traditional cancer treatments, as its activity has been linked to the durability of drug-resistant cell states,” states Professor Pedro Friedmann Angeli, head of Translational Cell Biology at the University of Würzburg (JMU), Germany. “However, by inhibiting GPX4 production, we might effectively target and eliminate cancer cells. This is especially promising for treating neuroblastoma, a cancer that primarily affects children.”
Making Cancer Cells More Vulnerable
In collaboration with researchers from the Heidelberg Institute for Stem Cell Technology and Experimental Medicine, led by junior group leader Hamed Alborzinia, Friedmann Angeli’s team is investigating ways to inhibit enzymes that assist in incorporating selenocysteine into selenoproteins. “Previously, we were aware of just one enzyme, selenocysteine lyase (SCLY), responsible for detaching the selenium atom from selenocysteine,” explains Zhiy Chen, a PhD student in Friedmann Angeli’s group and the lead author of the study. “Our research has revealed a new pathway that relies on the enzyme peroxiredoxin 6 (PRDX6), which supports the production of selenoproteins even without SCLY.”
Utilizing advanced techniques like mass spectrometry and CRISPR-Cas9-based functional genomics, the research group found that PRDX6 directly binds to selenium and functions as a transporter for the trace element, facilitating the formation of new selenoproteins. The study further indicated that inhibiting PRDX6 could reduce cancer cell survival, particularly in neuroblastomas, providing a promising new target for therapy.
Next Steps in Cancer Research
Interestingly, the researchers noted that while PRDX6 can compensate for the lack of SCLY, it does not possess the specific ability found in SCLY to extract the selenium atom from its precursors. Friedmann Angeli’s team plans to explore which other proteins work alongside PRDX6 to support selenium protein synthesis. Furthermore, they are looking to develop molecular inhibitors that target both SCLY and PRDX6, with the aim of more effectively impeding cancer cell proliferation.
This research involved collaboration with partners from the University of São Paulo in Brazil, the Institute of Stem Cell Technology and Experimental Medicine in Heidelberg, and the German Cancer Research Center (DKFZ). Financial backing came from the Rudolf Virchow Center at the University of Würzburg, the German Research Foundation (DFG), the EU-H2020 (ERC-CoG, DeciFERR), and the José Carreras Leukemia Foundation.
