The large tumor suppressor family: friend or foe?

In the past few years, Hippo signaling cascade has been a hotspot for scientists who work in the area of cell biology, especially cancer cell biology (1-4). The core components of this pathway in mammalian cells consist of MST1/2 (STE20-like protein kinase 1), MAP4Ks (mitogen-activated protein kinase kinase kinase kinases) and LATS1/2 (the large tumor suppressor 1/2) (5). During the activation of this pathway, LATS1/2 is phosphorylated and activated by MST1/2 or MAP4K family, which directly induces the phosphorylation of YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif). YAP and TAZ lie in the center of Hippo, so their phosphorylation prevents themselves from translocation into the nucleus and therefore stops conveying signals to the downstream (6).