The Hippo signaling pathway and translational opportunities for brain cancers

Merlin/NF2 tumor suppressor protein is a cytoskeleton-binding protein that modulates the activity of the Hippo pathway [5]. Investigating the activity of YAP1 in the mouse liver, Zhang and colleagues defined a functional role between Merlin/NF2 tumor suppressor and the Hippo pathway. The inactivation of Nf2 in the mouse liver led to YAP1 activation and to the formation of hepatocellular carcinoma [6]. Loss of NF2 tumor suppressor gene is a wellcharacterized genetic alteration in several cancers, largely in cancers of the CNS [7], prompting the attention on the importance of the Hippo pathway in the development of these cancers. In meningiomas, loss of Merlin activity is also associated with nuclear localization and YAP1 activation, and leads to the development of cells with a characteristic transformed phenotype [8]. In addition, deregulation of the Hippo pathway seems to be associated with several human cancers not associated with NF2 loss. Genetic and epigenetic mechanisms