Summary

We are mainly interested in the function of two transcription factors, which are altered in more than 50% of all human tumors: c-MYC and p53. In line with their opposing functions, they are encoded by a proto-oncogene (c-MYC) and a tumor suppressor gene (p53). The majority of colorectal cancer show activation of c-MYC by mutation in the b-catenin/APC pathway and mutational inactivation of p53. In the past, we identified important functional connections between these factors, such as the mediation of c-MYC-induced apoptosis by p53. In addition, we identified and characterized critical effectors of p53 and c-MYC, such as 14-3-3sigma, the miR-34 family of microRNAs (p53) and the BR-HLH-LZ TF AP4 and ZNF281 (c-MYC). Currently, we are studying the biology of these genes in mouse models of colorectal cancer. A focus of the lab is the regulation of metastatic progression as we could show that these factor are involved in the regulation of EMT (epithelial-mesenchymal transition) and its reversal, MET. In addition, we are studying the role of the networks mentioned above in the tumor microenvironment and tumor stem cell biology.