This work combined loss-of-function screening data mined from Project Achilles, a project partially supported by CTD², and gene expression/copy number analyses from the Cancer Cell Line Encyclopedia, with new β-catenin activity data across 85 cell lines. The integration of these data types allowed identification of 50 genes upon which β-catenin dependent cells preferentially rely for survival, including a number of genes related to the transcriptional regulator YAP1. Indeed, YAP1 was also required for tumor growth in a β-catenin dependent orthotopic colon tumor model. By further characterizing YAP1/β-catenin-mediated transformation, the group was able to find several factors linked to YAP1 that appear to be targetable with small molecules and might be suitable for use in future therapies.