Hippo on the move

Hippo and its mammalian homologs MST1 and MST2 are important tumor suppressors best known for their effects on cell proliferation and survival; however, accumulating evidence suggests that these kinases are involved in a wide range of cellular processes, including regulation of cell morphology, adhesion and migration. In the canonical pathway activated Hippo/ MST1/2 kinase phosphorylates and activates Warts/LATS kinase, which phosphorylates a transcriptional co-activator Yorkie (Yki) /YAP, retaining it in the cytoplasm. In the unphosphorylated state, Yki/ YAP translocates to the nucleus and drives transcription of various genes involved in cell cycle progression (Fig. 1). The function of Hippo/MST1/2 in processes other than growth control is less clear and appears to be cell type-specific. For example, in HeLa and NIH-3T3 cell lines, activation of MST1 induces cell rounding and detachment, while in T-cells inactivation of MST1 leads to similar phenotypes. Furthermore, it is unclear whether these growth-independent actions of Hippo/ MST1/2 rely on gene transcription. Using an unbiased screen for genes involved in chemotaxis of Dictyostelium discoideum, we identified Hippo/MST1/2 homolog KrsB as a novel regulator of multicellular pattern formation, cell substrate adhesion and directed migration (Fig. 1). Cells lacking KrsB kinase activity have increased contact with the substrate and are difficult to detach from the surface. This underlies defects in chemotaxis and random motility, which are corrected when cells are plated on a “slippery” Hippo on the move Tumor suppressor regulates adhesion and migration