Merlin, the Hippo Pathway, and Tumor Suppression in Meningiomas

摘要

The goal of this proposal was to determine whether merlin exerts its tumor suppressive effects in meningiomas by signaling through the Hippo pathway. Using paired meningioma cell lines, where the only difference is expression of merlin, we have shown that loss of merlin is associated with a clear increase in the protein levels of YAP, a transcriptional coactivator and downstream effector of the Hippo pathway. In addition to this increase, merlin loss was associated with nuclear localization of YAP. Using RNA interference and flow cytometry, we have shown that depletion of YAP results in a reversal of the enhanced proliferation phenotype caused by the loss of merlin. Thus, Merlin signals through YAP, a core component of the Hippo pathway, to regulate cell proliferation in meningiomas.