P-Catenin (Armadillo in Drosophila) is a multifunctional protein involved in both cell-cell adhesion and Wnt signaling. As an essential co-activator downstream of Wnt signaling, P-catenin regulates many biological processes essential for proper embryonic development and adult homeostasis. Once abnormally activated in adult tissues, however, P-catenin could contribute to the onset of tumorigenesis or accelerate tumor growth. In recent years, a variety of novel P-catenin interactors has been identified, highlighting P-catenin's role as the hub of a very complex network of protein-protein interactions that fine-tune its transcriptional activity. These molecular interactions, therefore, represent attractive targets for pharmacological intervention. Here, we provide an overview of P-catenin signaling in tumor formation, summarize recent advances in pharmacological strategies to inhibit P-catenin transcriptional output and explore new opportunities for drug discovery in targeting oncogenic P-catenin.

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