The roles of the Hippo pathway in cancer metastasis

Cancer metastasis refers to the sequence of events whereby tumour cells detach from their primary tissue, invade and migrate to nearby vasculature, intravasate into circulation, survive in circulation and extravasate at a distant site to establish a secondary tumour. Each step in this "metastatic cascade" is coordinated by complex molecular events that remain only incompletely understood. Given that the vast majority of cancer fatalities occur due to metastasis, there is an urgent need for an improved understanding of the specific mechanisms underlying cancer metastasis and for the development of therapeutics targeting this lethal process. The Hippo pathway is an emerging signaling pathway that plays important roles in development and disease. In cancer cells, dysregulation of the Hippo pathway drives multiple aspects of tumour initiation and progression. Recent studies have uncovered a role for the Hippo pathway core components in promoting cancer metastasis. In this review, we summarize the clinical and biochemical evidence implicating the Hippo pathway in metastasis. Additionally, we describe the molecular mechanisms by which aberrant Hippo signaling promotes metastasis. Finally, we highlight areas for future research.