Interaction partners of the oncogenic transcriptional repressor ZEB1 as targets to interfere with its oncogenic functions

Prof. Dr. Thomas Brabletz (Dept. of Visceral Surgery and Comprehensive Cancer Center, University Medical Centre)

Our aim is to identify new interaction partners of the EMT-activator and transcriptional repressor ZEB1, in order to specifically interfere with its tumor initiating and metastasis promoting function.

We have shown that ZEB1 is a master regulator of the epithelial-mesenchymal transition (EMT), a developmental process reactivated in cancer, which induces metastasis. By identifying a regulatory feedback-loop between ZEB1 and the miR-200 family, we could show that ZEB1 expression leads to persistence of a cancer stem cell-, drug resistance- and pro-metastatic phenotype. Thus inhibition of ZEB1 function is a promising therapeutic strategy to fight cancer drug resistance and progression toward metastasis.

However, since ZEB1 as transcription factor can not be targeted directly we search for necessary interaction partners as potential drug targets to interfere with its oncogenic functions. The project meets the central goals of BIOSS-2: It aims at identifying and characterizing new interaction partners of an oncogenic transcription factor. This will be the basis for future therapeutic interference to fight cancer metastasis and drug resistance.