EMT-dependent transcriptional enhancers important for metastatic colonisation (A04)

• Subject Area: Hematology, Oncology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 429280966

Tumour cell plasticity is a crucial feature for metastatic colonisation. The EMT-transcription factor Zeb1 is mediating this plasticity, and driving colonisation and metastasis, a process accompanied by substantial enhancer reprogramming. Zeb1 knock-out cell lines from a genetic mouse model of pancreatic cancer (KPC) are trapped in an epithelial phenotype and exhibit very low lung colonisation capacity compared to plastic Zeb1 wt lines. Since Zeb1 functions as a transcriptional co-activator mainly in putative enhancer regions, we aim to characterise the enhancer landscape of the above-mentioned cell lines to identify Zeb1 dependent enhancers and their target genes and test their relevance for colonisation and metastasis. We will validate our findings in human cell lines and organoids, thus advancing our understanding about molecular mechanisms of metastasis, which will provide the prospect of novel prognostic tools and putative targets for therapeutic strategies.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 305: Striking a moving target: From mechanisms of metastatic colonization to novel systemic therapies
• Applicant Institution: Universität Regensburg
• Project Heads: Dr. Simone Brabletz; Dr. Christian Schmidl