Regulation of the Hippo pathway and implications for anticancer drug development

• We outline identified upstream regulators and modular structures of the Hippo pathway.
• We propose anticancer drug targets in the Hippo pathway.

Research in the past decade has revealed key components of the Hippo tumor suppressor pathway and its critical role in organ size regulation and tumorigenesis. Recent progress has identified a wide range of upstream factors that control the Hippo pathway, which include cell–cell contact, various diffusible signals, and cognate receptors. Dysregulation of the Hippo pathway, caused by gene mutation or aberrant expression, promotes cell proliferation and tumorigenesis. Here, we discuss the current state of Hippo pathway research, primarily focusing on upstream regulators and protein–protein interactions as potential therapeutic targets. Consideration of pharmacological intervention of the Hippo pathway may provide novel avenues for future therapeutic treatment of human diseases, particularly in cancer.