Selenoproteins open up new strategies for treating certain cancers in children

Selenoproteins are important for several biological functions, including breaking down harmful substances, supporting the immune system, and regulating metabolic processes. However, in certain situations, these proteins can be exploited to protect cancer cells from death. One such protein, glutathione peroxidase 4 (GPX4), is essential for supporting cellular protection and cancer cell survival.

“This protective property of GPX4 poses a major challenge for standard cancer treatments, as its activity has been shown to promote survival in drug-resistant states,” said Translated by the University of Würzburg (JMU). says Pedro Friedman Angeli, National Professor of Cell Biology. ,Germany.

“However, if we can inhibit the production of GPX4, we may be able to target and destroy cancer cells. This is particularly promising for the treatment of neuroblastoma, which primarily affects children.”

Therefore, together with researchers from the Heidelberg Institute for Stem Cell Technology and Experimental Medicine, led by junior group leader Hamed Alborginia, Friedman Angeli’s team focused on investigating the inhibition of the enzyme that promotes the insertion of selenocysteine ​​into selenoproteins. I’m guessing.

The paper will be published in the journal Molecular Cell.

“Until now, only one enzyme, selenocysteine ​​lyase (SCLY), was responsible for releasing selenium atoms from selenocysteine,” explains Zhiy Chen, Ph.D. student on Friedman-Angeli’s team and lead author of the study.

“Our study identified an unexpected pathway that requires the enzyme peroxiredoxin 6 (PRDX6), which can maintain selenoprotein production in the absence of SCLY.”

Through cutting-edge techniques such as mass spectrometry and CRISPR-Cas9-based functional genomics, the research team found that PRDX6 binds directly to selenium, acts as a trace element transporter, or “shuttle,” and drives the production of new selenoproteins. I discovered that it is possible. . This study also demonstrated that inhibiting PRDX6 can impair cancer cell survival, particularly in neuroblastoma, and may represent a new potential therapeutic target.

Interestingly, the researchers found that while PRDX6 was able to compensate for the lack of SCLY, it lacked the specific activity present in SCLY that is required to remove selenium atoms from the precursor. Friedman-Angeli’s group aims to investigate which other proteins cooperate with PRDX6 to maintain selenoprotein synthesis. Furthermore, the development of molecular inhibitors targeting both SCLY and PRDX6 is on the horizon with the aim of more effectively inhibiting cancer cell proliferation.

The study was carried out in 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).