This group has a longstanding expertise in the molecular analysis of epithelial morphogenesis and differentiation, with emphasis on the cell adhesion and signal transduction functions of proteins placed in the E-cadherin/ catenin pathway. Especially the extension of this work to the characterisation of malignant, metastasizing colon tumors proved to be of direct medical importance. This work, in collaboration with Prof. Schlag of the Robert Roessle Cancer Center, was made possible by accessing tissue samples from a comprehensive tumor bank that was established at our research center. The collection features more than 10.000 samples, mostly derived from patients with a complete clinical follow-up and will enable us to address different aspects of tissue specificity in metastasis. In addition, Drosophila and zebrafish will be used as model organisms to unravel mechanisms and identify those genes involved in the initiation and manifestation of cancer. In Drosophila, we will embark on a strategy to identify genes involved in genome instability (M.G.), one of the defining features of tumor cells. In a parallel project, we will combine the advantages of the zebrafish in mutagenesis screening and developmental biology (S.A.-S.) with recent advances in cell biological and transgenesis methods (Z.I.), in an extensive gene discovery project for novel tumor genes.