The Hippo pathway defines a novel signaling cascade regulating cell 
proliferation and survival in Drosophila, which involves the negative regulation 
of the transcriptional coactivator Yorkie by the kinases Hippo and Warts. We 
have recently shown that the human ortholog of Yorkie, YAP, maps to a minimal 
amplification locus in mouse and human cancers, and that it mediates dramatic 
transforming activity in MCF10A primary mammary epithelial cells. Here, we show 
that LATS proteins (mammalian orthologs of Warts) interact directly with YAP in 
mammalian cells and that ectopic expression of LATS1, but not LATS2, effectively 
suppresses the YAP phenotypes. Furthermore, shRNA-mediated knockdown of LATS1 
phenocopies YAP overexpression. Because this effect can be suppressed by 
simultaneous YAP knockdown, it suggests that YAP is the primary target of LATS1 
in mammalian cells. Expression profiling of genes induced by ectopic expression 
of YAP or by knockdown of LATS1 reveals a subset of potential Hippo pathway 
targets implicated in epithelial-to-mesenchymal transition, suggesting that this 
is a key feature of YAP signaling in mammalian cells.