YAP-mediated induction of monoacylglycerol lipase restrains oncogenic transformation.

The Hippo pathway is an evolutionarily conserved regulator of normal and oncogenic growth. Engagement of Hippo pathway signaling results in the inactivation of the transcriptional coactivator YAP by preventing its nuclear entry. The mechanisms underlying the oncogenic properties of YAP remain incompletely understood. Here we find that although the transactivation (TA) domain of YAP mediates YAP-dependent gene expression, it serves as an inhibitor of YAP-mediated anchorage-independent growth. We identify monoacylglycerol lipase (MAGL) as a YAP transcriptional target and an inhibitor of anchorage-dependent cell growth. Significantly, knockdown of MAGL expression leads to the augmentation of YAP-dependent cell transformation. Our results identify MAGL as a transcriptional target of YAP that restrains YAP-mediated cellular transformation.