br STAR Methods br Acknowledgments We thank P Adler

STAR★Methods
Acknowledgments We thank P. Adler, V. Riechmann, N. Tapon, E. Knust, the Vienna Drosophila RNAi Center, the Australian Drosophila Research Support Facility (www.ozdros.com), the Bloomington Drosophila Stock Center, and the Developmental Studies Hybridoma Bank for D. melanogaster stocks and antibodies. We thank the Centre for Advanced Histology and Microscopy at the Peter MacCallum Cancer Centre. H. Zhao provided help with SAINT analysis. K.F.H. is a National Health and Medical Research Council Senior Research Fellow (1078220). A.V. was supported by a grant from the National Institutes of Health (GM123136). Y.K. was sponsored by the Ministry of National Education (The Republic of Turkey). This research was supported by the Peter MacCallum Cancer Foundation and grants from the National Health and Medical Research Council of Australia (K.F.H. – 1032251 and C.L.C.P. – 1142469), the Company of Biologists (Development Journal) Travelling Fellowship (C.L.C.P.) (Harvey laboratory), the National Institutes of Health (1R01GM089782), the American Cancer Society (ACS) (RSG 124720) (Ghabrial laboratory), the Wellcome Trust (090090/Z/09/Z), and BBSRC (BB/I021248/1) (Hergovich laboratory).
Introduction After the discovery of Hippo components in Drosophila, this kinase cassette has become an entry point for researchers to explain the organ-size controlling mechanism from a novel angle, whose dysfunction acts as an CFTRinh-172 sale clue for oncogenesis. Yet, the involvement of Hippo signaling also includes immunological aspects. A growing number of studies have delineated the branches of Hippo in immune events, and even cancer immunology, which gradually gives rise to the exploitation of immune-related anti-cancer therapeutics. While still in an infant stage, the landscape of Hippo cascade is expanding gradually.
At the very beginning, four members in this pathway were identified in Drosophila: Warts (Wts) [1] Salvador (Sav) [2], Hippo (Hpo) [3,4] and Mob-as-tumor-suppressor (Mats) [5]. Inactivation of any of these four members results in enhanced cellular growth and declining apoptosis, ending up with uncontrolled tissue proliferation. Functionally, Wts-Mats kinase is phosphorylated by Hpo-Sav complex, which activates this tumor-suppressive pathway. In the same period, the center of this pathway Yorkie (Yki) was discovered as well [6], whose activation, resembling invalid Wts/Mats-Hpo-Sav axis, led to massive proliferation. Ever since then, a basic concept was formed among people that, Hpo-Sav-induced phosphorylated Wts caused Yki phosphorylation, which increased mobility shift to control tissue growth. Later on, this transduction pattern was also proved to be applied to this “Hippo signaling” in mammalian cells. An exemplification has been well established ever since these findings in Drosophila were published. From the identification of its key compositions and its functions in keeping homeostasis to the translational potentials that lie behind, more and more studies have centered on Hippo pathway in mammals during the past decades [7,8]. In mammalian cells, counterparts of each core component have been revealed: MST1/2 for Hpo, SAV1 for Sav, LATS1/2 for Wts, MOB1 for Mats, and YAP/TAZ for Yki. Analogously, they form a kinase cascade [[9], [10], [11]], and systematically, YAP/TAZ is phosphorylated and isolated from the nucleus when dense cells adhere to each other [[12], [13], [14]], while cell detachment inactivates Hippo but promotes the YAP/TAZ translocation [13]. YAP and TAZ (Yki in Drosophila) locate in the central position of Hippo pathway, of which only one of them serves as a predominant transcriptional co-activator. Via its nuclear-cytoplasmic translocation, YAP or TAZ decides whether Hippo is effectively activated. As a conserved kinase cascade, Hippo is still among a myriad of mechanisms that regulate cell or tissue expansion in mammals. In fact, many of the molecular inspections have firmly characterized the roles of Hippo in fighting against neoplasia. For instance, demonstrated by multiple transgenic and knockout experiments, overabundant YAP [12,15], silenced MST1/2 [16,17] or SAV1 knockout [18,19] caused hepatomegaly and eventually led to hepatocellular carcinoma (HCC).