Bioinformatics approach to establish a new graph-based Wnt model for metastasis formation in breast cancer

• Antragsteller: Professor Dr. Tim Beißbarth
• Fachliche Zuordnung: Hämatologie, Onkologie
• Förderung: Förderung von 2011 bis 2015
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 45707573

WNT signaling occurs via β-catenin dependent and independent pathways. Genes of the WNT pathway are overrepresented in all molecular subtypes of breast cancer primaries which later metastasize to the brain. Through the direct analysis of breast cancer brain metastases we have shown that β-catenin independent signaling is important in this context. However, the critical WNT ligand could not be identified and an exact model of the regulation of these events is still lacking. Thus, the aim of the project is to establish a bioinformatic model of WNT signaling and its different sub-pathways in breast cancer. The model will be described as a directed graph. This graph will contain the molecules important in β-catenin dependent and independent WNT signaling and its regulated targets as nodes (vertices) and the different types of molecular interactions or regulation mechanisms as edges. Available data do not allow a dynamic quantitative model, as frequently used in Systems Biology. We therefore plan to first develop a biologically focused qualitative model of WNT signaling. For this purpose, own biological data will be generated. These own data as well as external breast cancer datasets (gene-expression data from the GEO database and protein-protein interactions) will be integrated into the WNT model. The resulting model will consider the different sub-pathways of WNT signaling as well as dependencies. The clinical relevance of this graph-based WNT model will be evaluated using external data sets of breast cancer primaries and metastases. In collaboration with other subprojects (SPs) the established pathway activation approach will be applied to other models within the FOR 942.

• DFG-Verfahren: Forschungsgruppen
• Teilprojekt zu: FOR 942: WNT signalling in development and tumor progression
• Beteiligte Personen: Professorin Dr. Annalen Bleckmann; Dr. Florian Klemm