The Hippo tumour suppressor pathway is a complex signalling network that controls developmental tissue growth and is frequently deregulated in different human cancers. A key question in Hippo signalling is how the Hippo kinase (MST1/2 in mammals) is activated by upstream regulatory inputs to limit tissue growth. Using a genetic screen in Drosophila melanogaster, we identified the sterile 20-like kinase, Tao-1, as a novel Hippo pathway member that activates Hippo. Tao-1 controls various biological phenomena including microtubule dynamics, animal behaviour and brain development. Here, we describe a previously unappreciated role for Tao-1 as a regulator of epithelial tissue growth by modulating activity of the core Hippo pathway kinase cassette. Tao-1 functions together with Hippo to activate Warts-mediated repression of Yorkie. Tao-1's ability to control SWH pathway activity is evolutionarily conserved as human TAO1 can suppress activity of the Yorkie orthologue, YAP. Human TAO1 controls SWH pathway activity by phosphorylating, and activating, the Hippo orthologue, MST2. Importantly, given that Hippo pathway activity is subverted in many human cancers, our findings identify human TAO kinases (TAO1, TAO2 and TAO3) as candidate tumor suppressor genes.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4180. doi:1538-7445.AM2012-4180