Developing Strategies to Block Beta-Catenin Action in Signaling and Cell Adhesion During Carcinogenesis

摘要

To understand cancer, we must first understand normal cell behavior. Drosophila Armadillo (Arm) and its human homolog Beta-catenin are key players in adhesive junctions and in transduction of Wingless (Wg)/Wnt signals. Our working hypotheses are: 1) Several protein partners compete to bind Arm, and 2) Arm:dTCF activates Wg-responsive genes, while dTCF alone represses the same genes. Aim I is to understand how different partners compete with one another for binding Arm. Aim 2 focuses on how Arm and dTCF positively and negatively regulate Wg- responsive genes. In our Final Report last year, we reported significant progress on both Aims. Here we describe additional work we have accomplished during a final one-year no cost-extension. In this period, we have examined interaction of Wnt and JNK pathways and the role of the MAPK phosphates Puckered in this interaction.