Mediator Kinasen als möglicher Therapieansatz bei Dickdarmkrebs
Allgemeine Genetik und funktionelle Genomforschung
Zusammenfassung der Projektergebnisse
The work performed in this fellowship by Dr Marius Dannappel and his team has identified a novel function of Mediator kinases CDK8/19 in the intestinal tract as important regulators of intestinal secretory cell differentiation by controlling ATOH1 expression. Furthermore, we discovered that the Mediator complex interacts with the SWI/SNF complex, a chromatin remodelling complex that is widely dysregulated in cancer and other diseases. While we were not able to (completely) decipher the functional relevance of this interaction in health and disease, this will be the subject of future work. Using a mouse model of CRC, we discovered that CDK8/19 act as tumour suppressor in the intestinal tract in addition to the well-known oncogenic function of CDK8. Analysis of tumour samples suggests that tumour progression is not affected by CDK8/19 ablation, therefore we suspect that CDK8/19 have tumour suppressor functions during tumour initiation. Work in this direction is currently ongoing. Beyond the intestinal tract, we identified novel in vivo functions of Mediator kinases in the liver and the immune system.
