Interaction of the Hippo Pathway and Phosphatases in Tumorigenesis

SIMPLE SUMMARY: Recently, a group of genes called “Hippo” has been discovered that is critical for the development and progression of a wide types of cancers. Therefore, modulating the “Hippo” activity is one of the most important ways to stop cancer. In this review, we have summarized for the first-time recent research findings on the crosstalk between “Hippo” and another group of genes called phosphatases. We have also proposed future directions of this research field. Our review provides very useful information on targeting of Hippo-phosphatases interactions for more effective cancer therapies in the future. ABSTRACT: The Hippo pathway is an emerging tumor suppressor signaling pathway involved in a wide range of cellular processes. Dysregulation of different components of the Hippo signaling pathway is associated with a number of diseases including cancer. Therefore, identification of the Hippo pathway regulators and the underlying mechanism of its regulation may be useful to uncover new therapeutics for cancer therapy. The Hippo signaling pathway includes a set of kinases that phosphorylate different proteins in order to phosphorylate and inactivate its main downstream effectors, YAP and TAZ. Thus, modulating phosphorylation and dephosphorylation of the Hippo components by kinases and phosphatases play critical roles in the regulation of the signaling pathway. While information regarding kinase regulation of the Hippo pathway is abundant, the role of phosphatases in regulating this pathway is just beginning to be understood. In this review, we summarize the most recent reports on the interaction of phosphatases and the Hippo pathway in tumorigenesis. We have also introduced challenges in clarifying the role of phosphatases in the Hippo pathway and future direction of crosstalk between phosphatases and the Hippo pathway.