Somatic DNA copy number variations (CNVs) are prevalent in cancer and can drive cancer progression albeit with often uncharacterized roles in altering cell signaling states. We developed a computational approach to predict regulators of signaling from the integrative analysis of genomic and proteomic pan-cancer datasets. Among the predictions, we identified ARHGEF17 to be a regulator of hippo-signaling and performed (phospho)proteomics analysis to test these predictions.