892
Views
13
CrossRef citations to date
0
Altmetric
Review Article

Hippo signaling pathway in liver and pancreas: the potential drug target for tumor therapy

, , &
Pages 125-133 | Received 05 Sep 2014, Accepted 29 Oct 2014, Published online: 03 Dec 2014

References

  • Li MD, Li CM, Wang Z. The role of circadian clocks in metabolic disease. Yale J Biol Med 2012;85:387–401
  • Zaret KS, Grompe M. Generation and regeneration of cells of the liver and pancreas. Science 2008;322:1490–4
  • Dor Y, Stanger BZ. Regeneration in liver and pancreas: time to cut the umbilical cord? Sci STKE 2007;2007:pe66
  • Huang JB, Wu S, Barrera J, et al. The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila homolog of YAP. Cell 2005;122:421–34
  • Dong J, Feldmann G, Huang J, et al. Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell 2007a;130:1120–33
  • Low BC, Pan CQ, Shivashankar GV, et al. YAP/TAZ as mechanosensors and mechanotransducers in regulating organ size and tumor growth. FEBS Lett 2014;588:2663–70
  • Cappello S, Gray MJ, Badouel C, et al. Mutations in genes encoding the cadherin receptor-ligand pair DCHS1 and FAT4 disrupt cerebral cortical development. Nat Genet 2013;45:1300–8
  • Bossuyt W, Chen CL, Chen Q, et al. An evolutionary shift in the regulation of the Hippo pathway between mice and flies. Oncogene 2014;33:1218–28
  • Zhao B, Li L, Lu Q, et al. Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein. Genes Dev 2011;25:51–63
  • Zhou D, Conrad C, Xia F, et al. Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene. Cancer Cell 2009;16:425–38
  • Zhao B, Li L, Lei Q, Guan KL. The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version. Genes Dev 2010;24:862–74
  • Kanai F, Marignani PA, Sarbassova D, et al. TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins. EMBO J 2000;19:6778–91
  • Sansores-Garcia L, Atkins M, Moya IM, et al. Mask is required for the activity of the Hippo pathway effector Yki/YAP. Curr Biol 2013;23:229–35
  • Sidor CM, Brain R, Thompson BJ. Mask proteins are cofactors of Yorkie/YAP in the Hippo pathway. Curr Biol 2013;23:223–8
  • Zhao B, Lei QY, Guan KL. The Hippo-YAP pathway: new connections between regulation of organ size and cancer. Curr Opin Cell Biol 2008;20:638–46
  • Ijichi H. Development of basic research of pancreatic cancer: from genetically-engineered mouse models to bedside. Nihon Shokakibyo Gakkai Zasshi 2014;111:1561–9
  • St Johnston D, Ahringer J. Cell polarity in eggs and epithelia: parallels and diversity. Cell 2010;141:757–74
  • Thomas C, Strutt D. The roles of the cadherins fat and dachsous in planar polarity specification in drosophila. Dev Dyn 2012;241:27–39
  • Irvine KD. Integration of intercellular signaling through the Hippo pathway. Semin Cell Dev Biol 2012;23:812–17
  • Tanentzapf G, Tepass U. Interactions between the crumbs, lethal giant larvae and bazooka pathways in epithelial polarization. Nat Cell Biol 2013;5:46–52
  • Johnson K, Wodarz A. A genetic hierarchy controlling cell polarity. Nat Cell Biol 2003;5:12–14
  • Bilder D, Schober M, Perrimon N. Integrated activity of PDZ protein complexes regulates epithelial polarity. Nat Cell Biol 2013;5:53–8
  • Paramasivam M, Sarkeshik A, Yates JR, III et al. Angiomotin family proteins are novel activators of the LATS2 kinase tumor suppressor. Mol Biol Cell 2011;22:3725–33
  • Varelas X, Samavarchi-Tehrani P, Narimatsu M, et al. The crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-beta-SMAD pathway. Dev Cell 2010;19:831–44
  • Yoshihama Y, Sasaki K, Horikoshi Y, et al. KIBRA suppresses apical exocytosis through inhibition of aPKC kinase activity in epithelial cells. Curr Biol 2011;21:705–11
  • Buther K, Plaas C, Barnekow A, Kremerskothen, J. KIBRA is a novel substrate for protein kinase Czeta. Biochem Biophys Res Commun 2004;317:703–7
  • Cordenonsi M, Zanconato F, Azzolin L, et al. The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell 2011;147:759–72
  • Chen D, Sun Y, Wei Y, et al. LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic marker. Nat Med 2012;18:1511–17
  • Grzeschik NA, Parsons LM, Allott ML, et al. Lgl, aPKC, and Crumbs regulate the Salvador/Warts/Hippo pathway through two distinct mechanisms. Curr Biol 2010;20:573–81
  • Klezovitch O, Fernandez TE, Tapscott SJ, Vasioukhin V. Loss of cell polarity causes severe brain dysplasia in Lgl1 knockout mice. Genes Dev 2004;18:559–71
  • Moleirinho S, Chang N, Sims AH, et al. KIBRA exhibits MST-independent functional regulation of the Hippo signaling pathway in mammals. Oncogene 2013;32:1821–30
  • Silvis MR, Kreger BT, Lien WH, et al. Alpha-catenin is a tumor suppressor that controls cell accumulation by regulating the localization and activity of the transcriptional coactivator Yap1. Sci Signal 2011;4:ra33
  • Schlegelmilch K, Mohseni M, Kirak O, et al. Yap1 acts downstream of alpha-catenin to control epidermal proliferation. Cell 2011;144:782–95
  • Yi C, Troutman S, Fera D, et al. A tight junction-associated Merlin-angiomotin complex mediates Merlin’s regulation of mitogenic signaling and tumor suppressive functions. Cancer Cell 2011;19:527–40
  • Yi C, Shen Z, Stemmer-Rachamimov A, et al. The p130 isoform of angiomotin is required for Yap-mediated hepatic epithelial cell proliferation and tumorigenesis. Sci Signal 2013;6:ra77
  • Oka T, Remue E, Meerschaert K, et al. Functional complexes between YAP2 and ZO-2 are PDZ domain-dependent, and regulate YAP2 nuclear localization and signalling. Biochem J 2010;432:461–72
  • Zhao B, Li L, Wang L, et al. Cell detachment activates the Hippo pathway via cytoskeleton reorganization to induce anoikis. Genes Dev 2012;26:54–68
  • Mammoto A, Ingber DE. Cytoskeletal control of growth and cell fate switching. Curr Opin Cell Biol 2009;21:864–70
  • Wada K, Itoga K, Okano T, et al. Hippo pathway regulation by cell morphology and stress fibers. Development 2011;138:3907–14
  • Aragona M, Panciera T, Manfrin A, et al. A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors. Cell 2013;154:1047–59
  • Mana-capelli S, Paramasivam M, Dutta S, Mccollum D. Angiomotins link F-actin architecture to Hippo pathway signaling. Mol Biol Cell 2014;25:1676–85
  • King I, Heberlein U. Tao kinases as coordinators of actin and microtubule dynamics in developing neurons. Commun Integr Biol 2011;4:554–6
  • Xiao ZG, Liu H, Fu JP, et al. Cloning of common carp SOCS-3 gene and its expression during embryogenesis, GH-transgene and viral infection. Fish Shellfish Immunol 2010;28:362–71
  • Poon CL, Lin JI, Zhang X, Harvey KF. The sterile 20-like kinase Tao-1 controls tissue growth by regulating the Salvador-Warts-Hippo pathway. Dev Cell 2011;21:896–906
  • Boggiano JC, Vanderzalm PJ, Fehon RG. Tao-1 phosphorylates Hippo/MST kinases to regulate the Hippo-Salvador-Warts tumor suppressor pathway. Dev Cell 2011;21:888–95
  • Rauskolb C, Sun S, Sun G, et al. Cytoskeletal tension inhibits Hippo signaling through an Ajuba-Warts complex. Cell 2014;158:143–56
  • Dupont S, Morsut L, Aragona M, et al. Role of YAP/TAZ in mechanotransduction. Nature 2011;474:179–83
  • Reddy BV, Irvine KD. Regulation of Hippo signaling by EGFR-MAPK signaling through Ajuba family proteins. Dev Cell 2013;24:459–71
  • Fan R, Kim NG, Gumbiner BM. Regulation of Hippo pathway by mitogenic growth factors via phosphoinositide 3-kinase and phosphoinositide-dependent kinase-1. Proc Natl Acad Sci USA 2013;110:2569–74
  • Yu FX, Zhao B, Panupinthu N, et al. Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell 2012;150:780–91
  • Miller E, Yang J, Deran M, et al. Identification of serum-derived sphingosine-1-phosphate as a small molecule regulator of YAP. Chem Biol 2012;19:955–62
  • Regue L, Mou F, Avruch J. G protein-coupled receptors engage the mammalian Hippo pathway through F-actin: F-Actin, assembled in response to Galpha12/13 induced RhoA-GTP, promotes dephosphorylation and activation of the YAP oncogene. Bioessays 2013;35:430–5
  • Serrano I, Mcdonald PC, Lock F, et al. Inactivation of the Hippo tumour suppressor pathway by integrin-linked kinase. Nat Commun 2013;4:2976–88
  • Macdonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 2009;17:9–26
  • Azzolin L, Panciera T, Soligo S, et al. YAP/TAZ incorporation in the beta-catenin destruction complex orchestrates the Wnt response. Cell 2014;158:157–70
  • Johnson R, Halder G. The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment. Nat Rev Drug Discov 2014;13:63–79
  • Zhao Y, Khanal P, Savage P, et al. YAP-induced resistance of cancer cells to antitubulin drugs is modulated by a Hippo-independent pathway. Cancer Res 2014;74:4493–503
  • Harvey KF, Zhang X, Thomas DM. The Hippo pathway and human cancer. Nat Rev Cancer 2013;13:246–57
  • Gomez M, Gomez V, Hergovich A. The Hippo pathway in disease and therapy: cancer and beyond. Clin Transl Med 2014;3:22–4
  • Dong J, Feldmann G, Huang J, et al. Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell 2007b;130:1120–33
  • Camargo FD, Gokhale S, Johnnidis J.B, et al. YAP1 increases organ size and expands undifferentiated progenitor cells. Curr Biol 2007;17:2054–60
  • Avruch J, Zhou D, Fitamant J, Bardeesy N. Mst1/2 signalling to Yap: gatekeeper for liver size and tumour development. Br J Cancer 2011;104:24–32
  • Bao Y, Nakagawa K, Yang Z, et al. A cell-based assay to screen stimulators of the Hippo pathway reveals the inhibitory effect of dobutamine on the YAP-dependent gene transcription. J Biochem 2011;150:199–208
  • Zender L, Spector MS, Xue W, et al. Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach. Cell 2006;125:1253–67
  • Jie L, Fan W, Weiqi D, et al. The hippo-yes association protein pathway in liver cancer. Gastroenterol Res Pract 2013;2013:187070
  • Zhang N, Bai H, David KK, et al. The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. Dev Cell 2010;19:27–38
  • Benhamouche S, Curto M, Saotome I, et al. Nf2/Merlin controls progenitor homeostasis and tumorigenesis in the liver. Genes Dev 2010;24:1718–30
  • Lee KP, Lee JH, Kim TS, et al. The Hippo-Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis. Proc Natl Acad Sci USA 2010;107:8248–53
  • Lu L, Li, Y, Kim SM, et al. Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver. Proc Natl Acad Sci USA 2010;107:1437–42
  • Alison MR. Liver stem cells: implications for hepatocarcinogenesis. Stem Cell Rev 2005;1:253–60
  • Yimlamai D, Christodoulou C, Galli GG, et al. Hippo pathway activity influences liver cell fate. Cell 2014;157:1324–38
  • Xiao W, Wang J, Ou C, et al. Mutual interaction between YAP and c-Myc is critical for carcinogenesis in liver cancer. Biochem Biophys Res Commun 2013;439:167–72
  • Wang J, Ma L, Weng W, et al. Mutual interaction between YAP and CREB promotes tumorigenesis in liver cancer. Hepatology 2013;58:1011–20
  • Wang J, Wang H, Zhang Y, et al. Mutual inhibition between YAP and SRSF1 maintains long non-coding RNA, Malat1-induced tumourigenesis in liver cancer. Cell Signal 2014;26:1048–59
  • Tschaharganeh DF, Chen X, Latzko P, et al. Yes-associated protein up-regulates Jagged-1 and activates the Notch pathway in human hepatocellular carcinoma. Gastroenterology 2013;144:1530–42.e12
  • Tao J, Calvisi DF, Ranganathan S, et al. Activation of beta-catenin and Yap1 in human hepatoblastoma and induction of hepatocarcinogenesis in mice. Gastroenterology 2014;147:690–701
  • Gittes GK. Developmental biology of the pancreas: a comprehensive review. Dev Biol 2009;326:4–35
  • Gu G, Dubauskaite J, Melton DA. Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development 2002;129:2447–57
  • Kawaguchi Y, Cooper B, Gannon M, et al. The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat Genet 2002;32:128–34
  • George NM, Day, CE, Boerner BP, et al. Hippo signaling regulates pancreas development through inactivation of Yap. Mol Cell Biol 2012;32:5116–28
  • Gao T, Zhou D, Yang C, et al. Hippo signaling regulates differentiation and maintenance in the exocrine pancreas. Gastroenterology 2013;144:1543–53, 1553 e1
  • Zhang ZW, Men T, Feng RC, et al. miR-375 inhibits proliferation of mouse pancreatic progenitor cells by targeting YAP1. Cell Physiol Biochem 2013;32:1808–17
  • Diep CH, Zucker KM, Hostetter G, et al. Down-regulation of Yes Associated Protein 1 expression reduces cell proliferation and clonogenicity of pancreatic cancer cells. PLoS One 2012;7:e32783
  • Almoguera C, Shibata D, Forrester K, et al. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 1988;53:549–54
  • Kong B, Qia C, Erkan M, et al. Overview on how oncogenic Kras promotes pancreatic carcinogenesis by inducing low intracellular ROS levels. Front Physiol 2013;4:246–55
  • Zhang W, Nandakumar N, Shi Y, et al. Downstream of mutant KRAS, the transcription regulator YAP is essential for neoplastic progression to pancreatic ductal adenocarcinoma. Sci Signal 2014;7:ra42
  • Huo X, Zhang Q, Liu AM, et al. Overexpression of Yes-associated protein confers doxorubicin resistance in hepatocellullar carcinoma. Oncol Rep 2013;29:840–6
  • Shimomura T, Miyamura N, Hata S, et al. The PDZ-binding motif of Yes-associated protein is required for its co-activation of TEAD-mediated CTGF transcription and oncogenic cell transforming activity. Biochem Biophys Res Commun 2014;443:917–23
  • Liu-Chittenden Y, Huang B, Shim JS, et al. Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. Genes Dev 2012;26:1300–5
  • Li XJ, Leem SH, Park MH, Kim SM. Regulation of YAP through an Akt-dependent process by 3,3′-diindolylmethane in human colon cancer cells. Int J Oncol 2013;43:1992–8
  • Jiao S, Wang H, Shi Z, et al. A peptide mimicking VGLL4 function acts as a YAP antagonist therapy against gastric cancer. Cancer Cell 2014;25:166–80
  • Basu D, Lettan R, Damodaran K, et al. Identification, mechanism of action, and antitumor activity of a small molecule inhibitor of hippo, TGF-beta, and Wnt signaling pathways. Mol Cancer Ther 2014;13:1457–67

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.