The Hippo Pathway as a Driver of Select Human Cancers

The Hippo pathway regulates myriad biological processes in diverse species and is a key cancer signaling network in humans. Although Hippo has been linked to multiple aspects of cancer, its role in this disease is incompletely understood. Large-scale pan-cancer analyses of core Hippo pathway genes reveal that the pathway is mutated at a high frequency only in select human cancers, including malignant mesothelioma and meningioma. Hippo pathway deregulation is also enriched in squamous epithelial cancers. We discuss cancer-related functions of the Hippo pathway and potential explanations for the cancer-restricted mutation profile of core Hippo pathway genes. Greater understanding of Hippo pathway deregulation in cancers will be essential to guide the imminent use of Hippo-targeted therapies.