FOR 942:  WNT Associated Signalling Pathways in Development and Tumour Progression

• Subject Area: Medicine
• Term: from 2007 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 45707573

Wnt proteins are secreted glycoproteins that after binding to their receptors activate several cellular pathways. Activation of the classical pathway inhibits the degradation of the structural and signal protein ß-Catenin. The second pathway involves Calcium influx, while the third regulates proteins that are primarily involved in modulation of cell structure and orientation/polarisation of cells in the tissue. The different signalling pathways should be seen in the context and not separately as the different proteins involved, regulate each other positively and negatively. A prediction about the biological effects of Wnt proteins when they bind to their receptors is not possible at present.
The different signalling pathways have a key role in embryonal development regulating cellular movement, division and orientation. In an adult organism they control tissue maintenance and regeneration, especially hematopoeisis and maintenance of bowel tissue. In a variety of cancers a defective regulation of theses genes has been described and Wnt pathways have been made partly responsable for the tumour development. More recent results even demonstrate that Wnt proteins are involved in tumour progression. They activate processes in adult cells that are normally only active during embryogenesis.
To further dissect these processes, this research network consists of specialists from developmental biology, immunology, human genetics, molecular oncology and hemato-oncology. By that, we are not only share our knowledge but also transfer technologies, that are used by the different participating groups. Furthermore, our combined knowledge will be of benefit for patients in the future by developing innovative ideas for new treatments.

• DFG Programme: Research Units

Projects

• Analyse der Funktion des kanonischen Wnt Signalweges bei der anterior-posterioren Musterbildung des Darmrohres in Xenopus Embryonen (Applicant Pieler, Tomas )
• Analyzing canoncical versus non-canoncical Wnt signalling in neural crest migration and differentiation (Applicants Borchers, Annette ;  Schambony, Alexandra )
• Bioinformatics approach to establish a new graph-based Wnt model for metastasis formation in breast cancer (Applicant Beißbarth, Tim )
• Central service project of the research group FOR 942 (Applicant Trümper, Lorenz )
• Chemoresistance as a consequence of Wnt-associated epithelial-mesenchymal transition (Applicant Dobbelstein, Matthias )
• Expression und Funktion von LEF-1, einem Signaturgen des molekularen Burkitt Lymphoms, in malignen Lymphomen (Applicant Kube, Dieter )
• Functional analysis of off track and CG8964, the Drosophila homologs of the vertebrate planar cell polarity gene PTK7 (Applicant Wodarz, Andreas )
• Interaction between Hh/Ptch and Wnt5a Signaling Pathways in Regression of Basal Cell Carcinoma (Applicant Hahn, Heidi )
• Regulation of Wnt signaling in macrophage-induced malignant invasion (Applicant Binder, Claudia )
• The role of the novel BCL9/BCL9-2 oncoproteins in tumorigenesis (Applicant Brembeck, Felix H. )
• The role of the Wnt signalling pathway for the maintenance of chromosomal stability (Applicant Bastians, Holger )

• Spokesperson: Professor Dr. Lorenz Trümper