ZNF827 – a protein with two faces: Essential for a healthy brain and cause of cancer metastases, University Medicine of the Johannes Gutenberg University Mainz, press release

An international research group, in which scientists from the I. Medical Clinic and Polyclinic and the Institute for Physiological Chemistry of the University Medical Center Mainz were involved, has identified a protein that is crucial for both the formation of healthy brain cells and the development of cancer metastases meaning is. The research team discovered that the protein ZNF827 regulates a mechanism in these two cellular processes that enables cell migration: the so-called epithelial-mesenchymal transition (EMT). The new findings on ZNF827, now published in the renowned journal “Nature Cell Biology”, might lead to earlier diagnosis and more targeted treatment of brain diseases and cancer.

During the epithelial-mesenchymal transition (EMT), epithelial cells that are firmly connected to the tissue develop into so-called mesenchymal cells. These have the special property of being able to hike. Little was previously known regarding the mechanisms that control EMT and the cell migration it enables. With their study, the researchers from Belfast (UK), La Jolla (USA), San Diego (USA), Montpellier (France), Stockholm (Sweden) and Mainz have now been able to prove that the zinc finger protein ZNF827 is primarily responsible for the regulation of EMT.

In the brain, EMT ensures that newly formed nerve cells move to a specific location and form an intact nerve network. If this migration process is disturbed, the nerve cells do not connect properly. As part of their research work, the scientists were able to show that if there is a deficiency in the protein ZNF827, fewer new nerve cells form and cell migration decreases significantly. If there is an excess of ZNF827, the cells develop too early. As a result, brain damage can occur. From these findings, the researchers conclude that the protein ZNF827 is an essential factor for healthy brain development.

The EMT mechanism also plays a key role in cancer. The tumor uses it to further develop, encapsulate and set in motion its cells. In this way, cancer cells can spread throughout the body and cause what is known as metastasis. Especially at a late stage of the cancer, EMT causes the tumor to grow aggressively and spread metastases. When examining breast cancer cells, the research team was able to prove that the protein ZNF827 – similar to the nerve cells in the brain – also plays a crucial role in determining the EMT of tumor cells: If there is a ZNF827 deficiency, the tumor grows only slowly and spreads fewer metastases to the lungs.

These new findings represent a significant advance in understanding the molecular processes involved in EMT. They open up new perspectives for innovative diagnostic and therapeutic approaches in brain diseases and various types of cancer.

The international research team included scientists from Queen’s University Belfast (UK), Salk Institute for Biological Studies (USA), Altos Labs (USA), Université de Montpellier (France), Karolinska Institutet (Sweden), Universitätsmedizin Mainz and Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz (TRON gGmbH). The study was supported by the German Research Foundation, the Wilhelm Sander Foundation and the “Innovation to Commercialization of University Research” program.

Originalpublikation:

Sahu S, Agirre E, Inayatullah M, Mahesh A, Tiwari N, Lavin DP, Singh A, Strand S, Diken M, Luco RF, Belmonte JCI, Tiwari VK, A complex epigenome-splicing crosstalk governs epithelial-to-mesenchymal transition in metastasis and brain development. Nature Cell Biology (2022).

DOI: https://doi.org/10.1038/s41556-022-00971-3