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Annual Review of Physiology

Volume 77, 2015

Hippo Pathway Regulation of Gastrointestinal Tissues

Abstract

The Hippo pathway plays a crucial role in regulating tissue homeostasis and organ size, and its deregulation is frequently observed in human cancer. Yap is the major effector of and is inhibited by the Hippo pathway. In mouse model studies, inducible Yap expression in multiple tissues results in organ overgrowth. In the liver, knockout of upstream Hippo pathway components or transgenic expression of Yap leads to liver enlargement and hepatocellular carcinoma. In the small intestine or colon, deletion of upstream Hippo pathway components also results in expansion of intestinal progenitor cells and eventual development of adenomas. Genetic deletion of Yap in the intestine does not change the intestinal structure, but Yap is essential for intestinal repair upon certain types of tissue injury. The function of the Hippo pathway has also been studied in other gastrointestinal tissues, including the pancreas and stomach. Here we provide a brief overview of the Hippo pathway and discuss the physiological and pathological functions of this tumor suppressor pathway in gastrointestinal tissues.

Keyword(s): cancer, intestine, liver, Mst1, Mst2, regeneration, Yap
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/content/journals/10.1146/annurev-physiol-021014-071733
2015-02-10
2024-04-18
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Literature Cited

  1. Wells JM, Melton DA. 1.  1999. Vertebrate endoderm development. Annu. Rev. Cell Dev. Biol. 15:393–410 [Google Scholar]
  2. van der Flier LG, Clevers H. 2.  2009. Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu. Rev. Physiol. 71:241–60 [Google Scholar]
  3. Michalopoulos GK. 3.  2010. Liver regeneration after partial hepatectomy: critical analysis of mechanistic dilemmas. Am. J. Pathol. 176:2–13 [Google Scholar]
  4. Pan D. 4.  2010. The Hippo signaling pathway in development and cancer. Dev. Cell 19:491–505 [Google Scholar]
  5. Tapon N, Harvey KF. 5.  2012. The Hippo pathway—from top to bottom and everything in between. Semin. Cell Dev. Biol. 23:768–9 [Google Scholar]
  6. Yu FX, Guan KL. 6.  2013. The Hippo pathway: regulators and regulations. Genes Dev. 27:355–71 [Google Scholar]
  7. Staley BK, Irvine KD. 7.  2012. Hippo signaling in Drosophila: recent advances and insights. Dev. Dyn. 241:3–15 [Google Scholar]
  8. Harvey KF, Pfleger CM, Hariharan IK. 8.  2003. The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis. Cell 114:457–67 [Google Scholar]
  9. Lai ZC, Wei X, Shimizu T, Ramos E, Rohrbaugh M. 9.  et al. 2005. Control of cell proliferation and apoptosis by Mob as tumor suppressor, Mats. Cell 120:675–85 [Google Scholar]
  10. Tapon N, Harvey KF, Bell DW, Wahrer DC, Schiripo TA. 10.  et al. 2002. salvador promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines. Cell 110:467–78 [Google Scholar]
  11. Wu S, Huang J, Dong J, Pan D. 11.  2003. hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts. Cell 114:445–56 [Google Scholar]
  12. Kango-Singh M, Nolo R, Tao C, Verstreken P, Hiesinger PR. 12.  et al. 2002. Shar-pei mediates cell proliferation arrest during imaginal disc growth in Drosophila. Development 129:5719–30 [Google Scholar]
  13. Xu T, Wang W, Zhang S, Stewart RA, Yu W. 13.  1995. Identifying tumor suppressors in genetic mosaics: The Drosophila lats gene encodes a putative protein kinase. Development 121:1053–63 [Google Scholar]
  14. Jia J, Zhang W, Wang B, Trinko R, Jiang J. 14.  2003. The Drosophila Ste20 family kinase dMST functions as a tumor suppressor by restricting cell proliferation and promoting apoptosis. Genes Dev. 17:2514–19 [Google Scholar]
  15. Justice RW, Zilian O, Woods DF, Noll M, Bryant PJ. 15.  1995. The Drosophila tumor suppressor gene warts encodes a homolog of human myotonic dystrophy kinase and is required for the control of cell shape and proliferation. Genes Dev. 9:534–46 [Google Scholar]
  16. Pantalacci S, Tapon N, Leopold P. 16.  2003. The Salvador partner Hippo promotes apoptosis and cell-cycle exit in Drosophila. Nat. Cell Biol. 5:921–27 [Google Scholar]
  17. Udan RS, Kango-Singh M, Nolo R, Tao C, Halder G. 17.  2003. Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway. Nat. Cell Biol. 5:914–20 [Google Scholar]
  18. Goulev Y, Fauny JD, Gonzalez-Marti B, Flagiello D, Silber J, Zider A. 18.  2008. SCALLOPED interacts with YORKIE, the nuclear effector of the Hippo tumor-suppressor pathway in Drosophila. Curr. Biol. 18:435–41 [Google Scholar]
  19. Wu S, Liu Y, Zheng Y, Dong J, Pan D. 19.  2008. The TEAD/TEF family protein Scalloped mediates transcriptional output of the Hippo growth-regulatory pathway. Dev. Cell 14:388–98 [Google Scholar]
  20. Zhang L, Ren F, Zhang Q, Chen Y, Wang B, Jiang J. 20.  2008. The TEAD/TEF family of transcription factor Scalloped mediates Hippo signaling in organ size control. Dev. Cell 14:377–87 [Google Scholar]
  21. Zhao B, Ye X, Yu J, Li L, Li W. 21.  et al. 2008. TEAD mediates YAP-dependent gene induction and growth control. Genes Dev. 22:1962–71 [Google Scholar]
  22. Huang J, Wu S, Barrera J, Matthews K, Pan D. 22.  2005. The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila homolog of YAP. Cell 122:421–34 [Google Scholar]
  23. Callus BA, Verhagen AM, Vaux DL. 23.  2006. Association of mammalian sterile twenty kinases, Mst1 and Mst2, with hSalvador via C-terminal coiled-coil domains, leads to its stabilization and phosphorylation. FEBS J. 273:4264–76 [Google Scholar]
  24. Chan EH, Nousiainen M, Chalamalasetty RB, Schafer A, Nigg EA, Sillje HH. 24.  2005. The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. Oncogene 24:2076–86 [Google Scholar]
  25. Praskova M, Xia F, Avruch J. 25.  2008. MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation. Curr. Biol. 18:311–21 [Google Scholar]
  26. Yin F, Yu J, Zheng Y, Chen Q, Zhang N, Pan D. 26.  2013. Spatial organization of Hippo signaling at the plasma membrane mediated by the tumor suppressor Merlin/NF2. Cell 154:1342–55 [Google Scholar]
  27. Dong J, Feldmann G, Huang J, Wu S, Zhang N. 27.  et al. 2007. Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell 130:1120–33 [Google Scholar]
  28. Lei QY, Zhang H, Zhao B, Zha ZY, Bai F. 28.  et al. 2008. TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the Hippo pathway. Mol. Cell. Biol. 28:2426–36 [Google Scholar]
  29. Oh H, Irvine KD. 29.  2008. In vivo regulation of Yorkie phosphorylation and localization. Development 135:1081–88 [Google Scholar]
  30. Zhao B, Wei X, Li W, Udan RS, Yang Q. 30.  et al. 2007. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev. 21:2747–61 [Google Scholar]
  31. Vassilev A, Kaneko KJ, Shu H, Zhao Y, DePamphilis ML. 31.  2001. TEAD/TEF transcription factors utilize the activation domain of YAP65, a Src/Yes-associated protein localized in the cytoplasm. Genes Dev. 15:1229–41 [Google Scholar]
  32. Adler JJ, Johnson DE, Heller BL, Bringman LR, Ranahan WP. 32.  et al. 2013. Serum deprivation inhibits the transcriptional co-activator YAP and cell growth via phosphorylation of the 130-kDa isoform of Angiomotin by the LATS1/2 protein kinases. Proc. Natl. Acad. Sci. USA 110:17368–73 [Google Scholar]
  33. Chan SW, Lim CJ, Guo F, Tan I, Leung T, Hong W. 33.  2013. Actin-binding and cell proliferation activities of angiomotin family members are regulated by Hippo pathway–mediated phosphorylation. J. Biol. Chem. 288:37296–307 [Google Scholar]
  34. Dai X, She P, Chi F, Feng Y, Liu H. 34.  et al. 2013. Phosphorylation of angiomotin by Lats1/2 kinases inhibits F-actin binding, cell migration, and angiogenesis. J. Biol. Chem. 288:34041–51 [Google Scholar]
  35. Hirate Y, Hirahara S, Inoue K, Suzuki A, Alarcon VB. 35.  et al. 2013. Polarity-dependent distribution of angiomotin localizes Hippo signaling in preimplantation embryos. Curr. Biol. 23:1181–94 [Google Scholar]
  36. Leung CY, Zernicka-Goetz M. 36.  2013. Angiomotin prevents pluripotent lineage differentiation in mouse embryos via Hippo pathway–dependent and –independent mechanisms. Nat. Commun. 4:2251 [Google Scholar]
  37. Anbanandam A, Albarado DC, Nguyen CT, Halder G, Gao X, Veeraraghavan S. 37.  2006. Insights into transcription enhancer factor 1 (TEF-1) activity from the solution structure of the TEA domain. Proc. Natl. Acad. Sci. USA 103:17225–30 [Google Scholar]
  38. Skibinski A, Breindel JL, Prat A, Galvan P, Smith E. 38.  et al. 2014. The Hippo transducer TAZ interacts with the SWI/SNF complex to regulate breast epithelial lineage commitment. Cell Rep. 6:1059–72 [Google Scholar]
  39. Couzens AL, Knight JD, Kean MJ, Teo G, Weiss A. 39.  et al. 2013. Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions. Sci. Signal. 6:rs15 [Google Scholar]
  40. Jin Y, Xu J, Yin MX, Lu Y, Hu L. 40.  et al. 2013. Brahma is essential for Drosophila intestinal stem cell proliferation and regulated by Hippo signaling. eLife 2:e00999 [Google Scholar]
  41. Oh H, Slattery M, Ma L, Crofts A, White KP. 41.  et al. 2013. Genome-wide association of Yorkie with chromatin and chromatin-remodeling complexes. Cell Rep. 3:309–18 [Google Scholar]
  42. Zhang W, Gao Y, Li P, Shi Z, Guo T. 42.  et al. 2014. VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEAD transcriptional complex. Cell Res. 24:331–43 [Google Scholar]
  43. Koontz LM, Liu-Chittenden Y, Yin F, Zheng Y, Yu J. 43.  et al. 2013. The Hippo effector Yorkie controls normal tissue growth by antagonizing Scalloped-mediated default repression. Dev. Cell 25:388–401 [Google Scholar]
  44. Halder G, Carroll SB. 44.  2001. Binding of the Vestigial co-factor switches the DNA-target selectivity of the Scalloped selector protein. Development 128:3295–305 [Google Scholar]
  45. Halder G, Polaczyk P, Kraus ME, Hudson A, Kim J. 45.  et al. 1998. The Vestigial and Scalloped proteins act together to directly regulate wing-specific gene expression in Drosophila. Genes Dev. 12:3900–9 [Google Scholar]
  46. Pobbati AV, Chan SW, Lee I, Song H, Hong W. 46.  2012. Structural and functional similarity between the Vgll1-TEAD and the YAP-TEAD complexes. Structure 20:1135–40 [Google Scholar]
  47. Jiao S, Wang H, Shi Z, Dong A, Zhang W. 47.  et al. 2014. A peptide mimicking VGLL4 function acts as a YAP antagonist therapy against gastric cancer. Cancer Cell 25:166–80 [Google Scholar]
  48. Liu-Chittenden Y, Huang B, Shim JS, Chen Q, Lee SJ. 48.  et al. 2012. Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. Genes Dev. 26:1300–5 [Google Scholar]
  49. Mori M, Triboulet R, Mohseni M, Schlegelmilch K, Shrestha K. 49.  et al. 2014. Hippo signaling regulates microprocessor and links cell-density-dependent miRNA biogenesis to cancer. Cell 156:893–906 [Google Scholar]
  50. Zhao B, Li L, Tumaneng K, Wang CY, Guan KL. 50.  2010. A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCFβ-TRCP. Genes Dev. 24:72–85 [Google Scholar]
  51. Kanai F, Marignani PA, Sarbassova D, Yagi R, Hall RA. 51.  et al. 2000. TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins. EMBO J. 19:6778–91 [Google Scholar]
  52. Liu CY, Zha ZY, Zhou X, Zhang H, Huang W. 52.  et al. 2010. The Hippo tumor pathway promotes TAZ degradation by phosphorylating a phosphodegron and recruiting the SCFβ-TrCP E3 ligase. J. Biol. Chem. 285:37159–69 [Google Scholar]
  53. Huang W, Lv X, Liu C, Zha Z, Zhang H. 53.  et al. 2012. The N-terminal phosphodegron targets TAZ/WWTR1 for SCFβ-TrCP dependent degradation in response to PI3K inhibition. J. Biol. Chem. 287:26245–53 [Google Scholar]
  54. Chen J, Verheyen EM. 54.  2012. Homeodomain-interacting protein kinase regulates Yorkie activity to promote tissue growth. Curr. Biol. 22:1582–86 [Google Scholar]
  55. Poon CL, Zhang X, Lin JI, Manning SA, Harvey KF. 55.  2012. Homeodomain-interacting protein kinase regulates Hippo pathway–dependent tissue growth. Curr. Biol. 22:1587–94 [Google Scholar]
  56. Yang S, Zhang L, Liu M, Chong R, Ding SJ. 56.  et al. 2013. CDK1 phosphorylation of YAP promotes mitotic defects and cell motility and is essential for neoplastic transformation. Cancer Res. 73:6722–33 [Google Scholar]
  57. Zhao Y, Khanal P, Savage P, She YM, Cyr TD, Yang X. 57.  2014. YAP-induced resistance of cancer cells to antitubulin drugs is modulated by a Hippo-independent pathway. Cancer Res. 74:4493–503 [Google Scholar]
  58. Baumgartner R, Poernbacher I, Buser N, Hafen E, Stocker H. 58.  2010. The WW domain protein Kibra acts upstream of Hippo in Drosophila. Dev. Cell 18:309–16 [Google Scholar]
  59. Genevet A, Wehr MC, Brain R, Thompson BJ, Tapon N. 59.  2010. Kibra is a regulator of the Salvador/Warts/Hippo signaling network. Dev. Cell 18:300–8 [Google Scholar]
  60. Hamaratoglu F, Willecke M, Kango-Singh M, Nolo R, Hyun E. 60.  et al. 2006. The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis. Nat. Cell Biol. 8:27–36 [Google Scholar]
  61. Yu J, Zheng Y, Dong J, Klusza S, Deng WM, Pan D. 61.  2010. Kibra functions as a tumor suppressor protein that regulates Hippo signaling in conjunction with Merlin and Expanded. Dev. Cell 18:288–99 [Google Scholar]
  62. Zhang N, Bai H, David KK, Dong J, Zheng Y. 62.  et al. 2010. The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. Dev. Cell 19:27–38 [Google Scholar]
  63. Moleirinho S, Chang N, Sims AH, Tilston-Lunel AM, Angus L. 63.  et al. 2013. KIBRA exhibits MST-independent functional regulation of the Hippo signaling pathway in mammals. Oncogene 32:1821–30 [Google Scholar]
  64. Angus L, Moleirinho S, Herron L, Sinha A, Zhang X. 64.  et al. 2012. Willin/FRMD6 expression activates the Hippo signaling pathway kinases in mammals and antagonizes oncogenic YAP. Oncogene 31:238–50 [Google Scholar]
  65. Sharma P, McNeill H. 65.  2013. Fat and Dachsous cadherins. Prog. Mol. Biol. Transl. Sci. 116:215–35 [Google Scholar]
  66. Chan SW, Lim CJ, Chong YF, Pobbati AV, Huang C, Hong W. 66.  2011. Hippo pathway–independent restriction of TAZ and YAP by angiomotin. J. Biol. Chem. 286:7018–26 [Google Scholar]
  67. Paramasivam M, Sarkeshik A, Yates JR 3rd, Fernandes MJ, McCollum D. 67.  2011. Angiomotin family proteins are novel activators of the LATS2 kinase tumor suppressor. Mol. Biol. Cell 22:3725–33 [Google Scholar]
  68. Wang W, Huang J, Chen J. 68.  2011. Angiomotin-like proteins associate with and negatively regulate YAP1. J. Biol. Chem. 286:4364–70 [Google Scholar]
  69. Zhao B, Li L, Lu Q, Wang LH, Liu CY. 69.  et al. 2011. Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein. Genes Dev. 25:51–63 [Google Scholar]
  70. Schlegelmilch K, Mohseni M, Kirak O, Pruszak J, Rodriguez JR. 70.  et al. 2011. Yap1 acts downstream of α-catenin to control epidermal proliferation. Cell 144:782–95 [Google Scholar]
  71. Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S. 71.  et al. 2011. Role of YAP/TAZ in mechanotransduction. Nature 474:179–83 [Google Scholar]
  72. Wada K, Itoga K, Okano T, Yonemura S, Sasaki H. 72.  2011. Hippo pathway regulation by cell morphology and stress fibers. Development 138:3907–14 [Google Scholar]
  73. Zhao B, Li L, Wang L, Wang CY, Yu J, Guan KL. 73.  2012. Cell detachment activates the Hippo pathway via cytoskeleton reorganization to induce anoikis. Genes Dev. 26:54–68 [Google Scholar]
  74. Fernandez BG, Gaspar P, Bras-Pereira C, Jezowska B, Rebelo SR, Janody F. 74.  2011. Actin-Capping Protein and the Hippo pathway regulate F-actin and tissue growth in Drosophila. Development 138:2337–46 [Google Scholar]
  75. Sansores-Garcia L, Bossuyt W, Wada K, Yonemura S, Tao C. 75.  et al. 2011. Modulating F-actin organization induces organ growth by affecting the Hippo pathway. EMBO J. 30:2325–35 [Google Scholar]
  76. Aragona M, Panciera T, Manfrin A, Giulitti S, Michielin F. 76.  et al. 2013. A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors. Cell 154:1047–59 [Google Scholar]
  77. Miller E, Yang J, Deran M, Wu C, Su AI. 77.  et al. 2012. Identification of serum-derived sphingosine-1-phosphate as a small molecule regulator of YAP. Chem. Biol. 19:955–62 [Google Scholar]
  78. Mo JS, Yu FX, Gong R, Brown JH, Guan KL. 78.  2012. Regulation of the Hippo-YAP pathway by protease-activated receptors (PARs). Genes Dev. 26:2138–43 [Google Scholar]
  79. Yu FX, Zhao B, Panupinthu N, Jewell JL, Lian I. 79.  et al. 2012. Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell 150:780–91 [Google Scholar]
  80. Kim M, Lee S, Kuninaka S, Saya H, Lee H, Lim DS. 80.  2013. cAMP/PKA signalling reinforces the LATS-YAP pathway to fully suppress YAP in response to actin cytoskeletal changes. EMBO J. 32:1543–55 [Google Scholar]
  81. Yu FX, Zhang Y, Park HW, Jewell JL, Chen Q. 81.  et al. 2013. Protein kinase A activates the Hippo pathway to modulate cell proliferation and differentiation. Genes Dev. 27:1223–32 [Google Scholar]
  82. Reddy BV, Irvine KD. 82.  2013. Regulation of Hippo signaling by EGFR-MAPK signaling through Ajuba family proteins. Dev. Cell 24:459–71 [Google Scholar]
  83. Fan R, Kim NG, Gumbiner BM. 83.  2013. Regulation of Hippo pathway by mitogenic growth factors via phosphoinositide 3-kinase and phosphoinositide-dependent kinase-1. Proc. Natl. Acad. Sci. USA 110:2569–74 [Google Scholar]
  84. Johnson R, Halder G. 84.  2014. The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment. Nat. Rev. Drug Discov. 13:63–79 [Google Scholar]
  85. Azzolin L, Zanconato F, Bresolin S, Forcato M, Basso G. 85.  et al. 2012. Role of TAZ as mediator of Wnt signaling. Cell 151:1443–56 [Google Scholar]
  86. Barry ER, Morikawa T, Butler BL, Shrestha K, de la Rosa R. 86.  et al. 2013. Restriction of intestinal stem cell expansion and the regenerative response by YAP. Nature 493:106–10 [Google Scholar]
  87. Varelas X, Miller BW, Sopko R, Song S, Gregorieff A. 87.  et al. 2010. The Hippo pathway regulates Wnt/β-catenin signaling. Dev. Cell 18:579–91 [Google Scholar]
  88. Imajo M, Miyatake K, Iimura A, Miyamoto A, Nishida E. 88.  2012. A molecular mechanism that links Hippo signalling to the inhibition of Wnt/β-catenin signalling. EMBO J. 31:1109–22 [Google Scholar]
  89. Heallen T, Zhang M, Wang J, Bonilla-Claudio M, Klysik E. 89.  et al. 2011. Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size. Science 332:458–61 [Google Scholar]
  90. Rosenbluh J, Nijhawan D, Cox AG, Li X, Neal JT. 90.  et al. 2012. β-Catenin-driven cancers require a YAP1 transcriptional complex for survival and tumorigenesis. Cell 151:1457–73 [Google Scholar]
  91. Varelas X, Sakuma R, Samavarchi-Tehrani P, Peerani R, Rao BM. 91.  et al. 2008. TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal. Nat. Cell Biol. 10:837–48 [Google Scholar]
  92. Ferrigno O, Lallemand F, Verrecchia F, L'Hoste S, Camonis J. 92.  et al. 2002. Yes-associated protein (YAP65) interacts with Smad7 and potentiates its inhibitory activity against TGF-β/Smad signaling. Oncogene 21:4879–84 [Google Scholar]
  93. Alarcon C, Zaromytidou AI, Xi Q, Gao S, Yu J. 93.  et al. 2009. Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-β pathways. Cell 139:757–69 [Google Scholar]
  94. Lai D, Yang X. 94.  2013. BMP4 is a novel transcriptional target and mediator of mammary cell migration downstream of the Hippo pathway component TAZ. Cell. Signal. 25:1720–28 [Google Scholar]
  95. Judson RN, Tremblay AM, Knopp P, White RB, Urcia R. 95.  et al. 2012. The Hippo pathway member Yap plays a key role in influencing fate decisions in muscle satellite cells. J. Cell Sci. 125:6009–19 [Google Scholar]
  96. Camargo FD, Gokhale S, Johnnidis JB, Fu D, Bell GW. 96.  et al. 2007. YAP1 increases organ size and expands undifferentiated progenitor cells. Curr. Biol. 17:2054–60 [Google Scholar]
  97. Zhou D, Zhang Y, Wu H, Barry E, Yin Y. 97.  et al. 2011. Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance. Proc. Natl. Acad. Sci. USA 108:E1312–20 [Google Scholar]
  98. Tschaharganeh DF, Chen X, Latzko P, Malz M, Gaida MM. 98.  et al. 2013. Yes-associated protein up-regulates Jagged-1 and activates the Notch pathway in human hepatocellular carcinoma. Gastroenterology 144:1530–42 [Google Scholar]
  99. Fernandez LA, Northcott PA, Dalton J, Fraga C, Ellison D. 99.  et al. 2009. YAP1 is amplified and up-regulated in hedgehog-associated medulloblastomas and mediates Sonic hedgehog–driven neural precursor proliferation. Genes Dev. 23:2729–41 [Google Scholar]
  100. Zhang J, Ji JY, Yu M, Overholtzer M, Smolen GA. 100.  et al. 2009. YAP-dependent induction of amphiregulin identifies a non-cell-autonomous component of the Hippo pathway. Nat. Cell Biol. 11:1444–50 [Google Scholar]
  101. Xin M, Kim Y, Sutherland LB, Qi X, McAnally J. 101.  et al. 2011. Regulation of insulin-like growth factor signaling by Yap governs cardiomyocyte proliferation and embryonic heart size. Sci. Signal. 4:ra70 [Google Scholar]
  102. Hossain Z, Ali SM, Ko HL, Xu J, Ng CP. 102.  et al. 2007. Glomerulocystic kidney disease in mice with a targeted inactivation of Wwtr1. Proc. Natl. Acad. Sci. USA 104:1631–36 [Google Scholar]
  103. Morin-Kensicki EM, Boone BN, Howell M, Stonebraker JR, Teed J. 103.  et al. 2006. Defects in yolk sac vasculogenesis, chorioallantoic fusion, and embryonic axis elongation in mice with targeted disruption of Yap65. Mol. Cell. Biol. 26:77–87 [Google Scholar]
  104. Nishioka N, Inoue K, Adachi K, Kiyonari H, Ota M. 104.  et al. 2009. The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass. Dev. Cell 16:398–410 [Google Scholar]
  105. Lorthongpanich C, Messerschmidt DM, Chan SW, Hong W, Knowles BB, Solter D. 105.  2013. Temporal reduction of LATS kinases in the early preimplantation embryo prevents ICM lineage differentiation. Genes Dev. 27:1441–46 [Google Scholar]
  106. Nishio M, Hamada K, Kawahara K, Sasaki M, Noguchi F. 106.  et al. 2012. Cancer susceptibility and embryonic lethality in Mob1a/1b double-mutant mice. J. Clin. Investig. 122:4505–18 [Google Scholar]
  107. Cockburn K, Biechele S, Garner J, Rossant J. 107.  2013. The Hippo pathway member Nf2 is required for inner cell mass specification. Curr. Biol. 23:1195–201 [Google Scholar]
  108. Lian I, Kim J, Okazawa H, Zhao J, Zhao B. 108.  et al. 2010. The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiation. Genes Dev. 24:1106–18 [Google Scholar]
  109. Qin H, Blaschke K, Wei G, Ohi Y, Blouin L. 109.  et al. 2012. Transcriptional analysis of pluripotency reveals the Hippo pathway as a barrier to reprogramming. Hum. Mol. Genet. 21:2054–67 [Google Scholar]
  110. Jansson L, Larsson J. 110.  2012. Normal hematopoietic stem cell function in mice with enforced expression of the Hippo signaling effector YAP1. PLOS ONE 7:e32013 [Google Scholar]
  111. Taub R. 111.  2004. Liver regeneration: from myth to mechanism. Nat. Rev. Mol. Cell Biol. 5:836–47 [Google Scholar]
  112. Fausto N, Campbell JS, Riehle KJ. 112.  2006. Liver regeneration. Hepatology 43:S45–53 [Google Scholar]
  113. Pitot HC. 113.  1998. Hepatocyte death in hepatocarcinogenesis. Hepatology 28:1–5 [Google Scholar]
  114. Bursch W, Paffe S, Putz B, Barthel G, Schulte-Hermann R. 114.  1990. Determination of the length of the histological stages of apoptosis in normal liver and in altered hepatic foci of rats. Carcinogenesis 11:847–53 [Google Scholar]
  115. Avruch J, Zhou D, Fitamant J, Bardeesy N. 115.  2011. Mst1/2 signalling to Yap: gatekeeper for liver size and tumour development. Br. J. Cancer 104:24–32 [Google Scholar]
  116. Zhou D, Conrad C, Xia F, Park JS, Payer B. 116.  et al. 2009. Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene. Cancer Cell 16:425–38 [Google Scholar]
  117. Song H, Mak KK, Topol L, Yun K, Hu J. 117.  et al. 2010. Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression. Proc. Natl. Acad. Sci. USA 107:1431–36 [Google Scholar]
  118. Lu L, Li Y, Kim SM, Bossuyt W, Liu P. 118.  et al. 2010. Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver. Proc. Natl. Acad. Sci. USA 107:1437–42 [Google Scholar]
  119. Lee KP, Lee JH, Kim TS, Kim TH, Park HD. 119.  et al. 2010. The Hippo-Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis. Proc. Natl. Acad. Sci. USA 107:8248–53 [Google Scholar]
  120. McPherson JP, Tamblyn L, Elia A, Migon E, Shehabeldin A. 120.  et al. 2004. Lats2/Kpm is required for embryonic development, proliferation control and genomic integrity. EMBO J. 23:3677–88 [Google Scholar]
  121. St John MA, Tao W, Fei X, Fukumoto R, Carcangiu ML. 121.  et al. 1999. Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction. Nat. Genet. 21:182–86 [Google Scholar]
  122. Yang X, Yu K, Hao Y, Li DM, Stewart R. 122.  et al. 2004. LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1. Nat. Cell Biol. 6:609–17 [Google Scholar]
  123. Yabuta N, Okada N, Ito A, Hosomi T, Nishihara S. 123.  et al. 2007. Lats2 is an essential mitotic regulator required for the coordination of cell division. J. Biol. Chem. 282:19259–71 [Google Scholar]
  124. Yi C, Shen Z, Stemmer-Rachamimov A, Dawany N, Troutman S. 124.  et al. 2013. The p130 isoform of angiomotin is required for Yap-mediated hepatic epithelial cell proliferation and tumorigenesis. Sci. Signal. 6:ra77 [Google Scholar]
  125. Tommasi S, Dammann R, Zhang Z, Wang Y, Liu L. 125.  et al. 2005. Tumor susceptibility of Rassf1a knockout mice. Cancer Res. 65:92–98 [Google Scholar]
  126. Arzumanyan A, Reis HM, Feitelson MA. 126.  2013. Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma. Nat. Rev. Cancer 13:123–35 [Google Scholar]
  127. Chuang SC, La Vecchia C, Boffetta P. 127.  2009. Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV infection. Cancer Lett. 286:9–14 [Google Scholar]
  128. He G, Karin M. 128.  2011. NF-κB and STAT3: key players in liver inflammation and cancer. Cell Res. 21:159–68 [Google Scholar]
  129. Tzameli I, Pissios P, Schuetz EG, Moore DD. 129.  2000. The xenobiotic compound 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene is an agonist ligand for the nuclear receptor CAR. Mol. Cell. Biol. 20:2951–58 [Google Scholar]
  130. Kowalik MA, Saliba C, Pibiri M, Perra A, Ledda-Columbano GM. 130.  et al. 2011. Yes-associated protein regulation of adaptive liver enlargement and hepatocellular carcinoma development in mice. Hepatology 53:2086–96 [Google Scholar]
  131. Zhang T, Zhang J, You X, Liu Q, Du Y. 131.  et al. 2012. Hepatitis B virus X protein modulates oncogene Yes-associated protein by CREB to promote growth of hepatoma cells. Hepatology 56:2051–59 [Google Scholar]
  132. Ilanges A, Jahanshahi M, Balobin DM, Pfleger CM. 132.  2013. Alcohol interacts with genetic alteration of the Hippo tumor suppressor pathway to modulate tissue growth in Drosophila. PLOS ONE 8:e78880 [Google Scholar]
  133. Bai H, Zhang N, Xu Y, Chen Q, Khan M. 133.  et al. 2012. Yes-associated protein regulates the hepatic response after bile duct ligation. Hepatology 56:1097–107 [Google Scholar]
  134. Gurda GT, Zhu Q, Bai H, Pan D, Schwarz KB, Anders RA. 134.  2014. The use of Yes-associated protein expression in the diagnosis of persistent neonatal cholestatic liver disease. Hum. Pathol. 45:1057–64 [Google Scholar]
  135. Anakk S, Bhosale M, Schmidt VA, Johnson RL, Finegold MJ, Moore DD. 135.  2013. Bile acids activate YAP to promote liver carcinogenesis. Cell Rep. 5:1060–69 [Google Scholar]
  136. Sasaki M, Matsubara T, Nitta T, Sato Y, Nakanuma Y. 136.  2013. GNAS and KRAS mutations are common in intraductal papillary neoplasms of the bile duct. PLOS ONE 8:e81706 [Google Scholar]
  137. Pols TW, Noriega LG, Nomura M, Auwerx J, Schoonjans K. 137.  2011. The bile acid membrane receptor TGR5 as an emerging target in metabolism and inflammation. J. Hepatol. 54:1263–72 [Google Scholar]
  138. Studer E, Zhou X, Zhao R, Wang Y, Takabe K. 138.  et al. 2012. Conjugated bile acids activate the sphingosine-1-phosphate receptor 2 in primary rodent hepatocytes. Hepatology 55:267–76 [Google Scholar]
  139. Zender L, Spector MS, Xue W, Flemming P, Cordon-Cardo C. 139.  et al. 2006. Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach. Cell 125:1253–67 [Google Scholar]
  140. Xu MZ, Yao TJ, Lee NP, Ng IO, Chan YT. 140.  et al. 2009. Yes-associated protein is an independent prognostic marker in hepatocellular carcinoma. Cancer 115:4576–85 [Google Scholar]
  141. Wang C, Zhang L, He Q, Feng X, Zhu J. 141.  et al. 2012. Differences in Yes-associated protein and mRNA levels in regenerating liver and hepatocellular carcinoma. Mol. Med. Rep. 5:410–14 [Google Scholar]
  142. Clavien PA, Petrowsky H, DeOliveira ML, Graf R. 142.  2007. Strategies for safer liver surgery and partial liver transplantation. N. Engl. J. Med. 356:1545–59 [Google Scholar]
  143. Clevers H. 143.  2013. The intestinal crypt, a prototype stem cell compartment. Cell 154:274–84 [Google Scholar]
  144. Li L, Clevers H. 144.  2010. Coexistence of quiescent and active adult stem cells in mammals. Science 327:542–45 [Google Scholar]
  145. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M. 145.  et al. 2007. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449:1003–7 [Google Scholar]
  146. Sato T, Vries RG, Snippert HJ. de Wetering M, Barker N. 146. , van et al. 2009. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459:262–65 [Google Scholar]
  147. Lee G, White LS, Hurov KE, Stappenbeck TS, Piwnica-Worms H. 147.  2009. Response of small intestinal epithelial cells to acute disruption of cell division through CDC25 deletion. Proc. Natl. Acad. Sci. USA 106:4701–6 [Google Scholar]
  148. Sangiorgi E, Capecchi MR. 148.  2008. Bmi1 is expressed in vivo in intestinal stem cells. Nat. Genet. 40:915–20 [Google Scholar]
  149. Tian H, Biehs B, Warming S, Leong KG, Rangell L. 149.  et al. 2011. A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature 478:255–59 [Google Scholar]
  150. Yan KS, Chia LA, Li X, Ootani A, Su J. 150.  et al. 2012. The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. Proc. Natl. Acad. Sci. USA 109:466–71 [Google Scholar]
  151. Crosnier C, Stamataki D, Lewis J. 151.  2006. Organizing cell renewal in the intestine: stem cells, signals and combinatorial control. Nat. Rev. Genet. 7:349–59 [Google Scholar]
  152. Madison BB, Braunstein K, Kuizon E, Portman K, Qiao XT, Gumucio DL. 152.  2005. Epithelial hedgehog signals pattern the intestinal crypt-villus axis. Development 132:279–89 [Google Scholar]
  153. Korinek V, Barker N, Moerer P, van Donselaar E, Huls G. 153.  et al. 1998. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat. Genet. 19:379–83 [Google Scholar]
  154. Kim KA, Kakitani M, Zhao J, Oshima T, Tang T. 154.  et al. 2005. Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science 309:1256–59 [Google Scholar]
  155. Haramis AP, Begthel H, van den Born M, van Es J, Jonkheer S. 155.  et al. 2004. De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine. Science 303:1684–86 [Google Scholar]
  156. Kosinski C, Li VS, Chan AS, Zhang J, Ho C. 156.  et al. 2007. Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors. Proc. Natl. Acad. Sci. USA 104:15418–23 [Google Scholar]
  157. Milano J, McKay J, Dagenais C, Foster-Brown L, Pognan F. 157.  et al. 2004. Modulation of notch processing by γ-secretase inhibitors causes intestinal goblet cell metaplasia and induction of genes known to specify gut secretory lineage differentiation. Toxicol. Sci. 82:341–58 [Google Scholar]
  158. van Es JH, van Gijn ME, Riccio O, van den Born M, Vooijs M. 158.  et al. 2005. Notch/γ-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature 435:959–63 [Google Scholar]
  159. Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG. 159.  et al. 2011. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469:415–18 [Google Scholar]
  160. He XC, Zhang J, Tong WG, Tawfik O, Ross J. 160.  et al. 2004. BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-β-catenin signaling. Nat. Genet. 36:1117–21 [Google Scholar]
  161. Casali A, Batlle E. 161.  2009. Intestinal stem cells in mammals and Drosophila. Cell Stem Cell 4:124–27 [Google Scholar]
  162. Lin G, Xu N, Xi R. 162.  2008. Paracrine Wingless signalling controls self-renewal of Drosophila intestinal stem cells. Nature 455:1119–23 [Google Scholar]
  163. Ohlstein B, Spradling A. 163.  2007. Multipotent Drosophila intestinal stem cells specify daughter cell fates by differential notch signaling. Science 315:988–92 [Google Scholar]
  164. Buchon N, Broderick NA, Chakrabarti S, Lemaitre B. 164.  2009. Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila. Genes Dev. 23:2333–44 [Google Scholar]
  165. Jiang H, Patel PH, Kohlmaier A, Grenley MO, McEwen DG, Edgar BA. 165.  2009. Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell 137:1343–55 [Google Scholar]
  166. Karpowicz P, Perez J, Perrimon N. 166.  2010. The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration. Development 137:4135–45 [Google Scholar]
  167. Ren F, Wang B, Yue T, Yun EY, Ip YT, Jiang J. 167.  2010. Hippo signaling regulates Drosophila intestine stem cell proliferation through multiple pathways. Proc. Natl. Acad. Sci. USA 107:21064–69 [Google Scholar]
  168. Shaw RL, Kohlmaier A, Polesello C, Veelken C, Edgar BA, Tapon N. 168.  2010. The Hippo pathway regulates intestinal stem cell proliferation during Drosophila adult midgut regeneration. Development 137:4147–58 [Google Scholar]
  169. Staley BK, Irvine KD. 169.  2010. Warts and Yorkie mediate intestinal regeneration by influencing stem cell proliferation. Curr. Biol. 20:1580–87 [Google Scholar]
  170. Huang H, Li J, Hu L, Ge L, Ji H. 170.  et al. 2014. Bantam is essential for Drosophila intestinal stem cell proliferation in response to Hippo signaling. Dev. Biol. 385:211–19 [Google Scholar]
  171. Cai J, Zhang N, Zheng Y, de Wilde RF, Maitra A, Pan D. 171.  2010. The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program. Genes Dev. 24:2383–88 [Google Scholar]
  172. Lee JH, Kim TS, Yang TH, Koo BK, Oh SP. 172.  et al. 2008. A crucial role of WW45 in developing epithelial tissues in the mouse. EMBO J. 27:1231–42 [Google Scholar]
  173. Cao X, Pfaff SL, Gage FH. 173.  2008. YAP regulates neural progenitor cell number via the TEA domain transcription factor. Genes Dev. 22:3320–34 [Google Scholar]
  174. Calvo F, Ege N, Grande-Garcia A, Hooper S, Jenkins RP. 174.  et al. 2013. Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nat. Cell Biol. 15:637–46 [Google Scholar]
  175. Ren F, Shi Q, Chen Y, Jiang A, Ip YT. 175.  et al. 2013. Drosophila Myc integrates multiple signaling pathways to regulate intestinal stem cell proliferation during midgut regeneration. Cell Res. 23:1133–46 [Google Scholar]
  176. Cordenonsi M, Zanconato F, Azzolin L, Forcato M, Rosato A. 176.  et al. 2011. The Hippo transducer TAZ confers cancer stem cell–related traits on breast cancer cells. Cell 147:759–72 [Google Scholar]
  177. Terzic J, Grivennikov S, Karin E, Karin M. 177.  2010. Inflammation and colon cancer. Gastroenterology 138:2101–14 [Google Scholar]
  178. Miyoshi Y, Ando H, Nagase H, Nishisho I, Horii A. 178.  et al. 1992. Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients. Proc. Natl. Acad. Sci. USA 89:4452–56 [Google Scholar]
  179. Powell SM, Zilz N, Beazer-Barclay Y, Bryan TM, Hamilton SR. 179.  et al. 1992. APC mutations occur early during colorectal tumorigenesis. Nature 359:235–37 [Google Scholar]
  180. Steinhardt AA, Gayyed MF, Klein AP, Dong J, Maitra A. 180.  et al. 2008. Expression of Yes-associated protein in common solid tumors. Hum. Pathol. 39:1582–89 [Google Scholar]
  181. Wang L, Shi S, Guo Z, Zhang X, Han S. 181.  et al. 2013. Overexpression of YAP and TAZ is an independent predictor of prognosis in colorectal cancer and related to the proliferation and metastasis of colon cancer cells. PLOS ONE 8:e65539 [Google Scholar]
  182. Yuen HF, McCrudden CM, Huang YH, Tham JM, Zhang X. 182.  et al. 2013. TAZ expression as a prognostic indicator in colorectal cancer. PLOS ONE 8:e54211 [Google Scholar]
  183. Touil Y, Igoudjil W, Corvaisier M, Dessein AF, Vandomme J. 183.  et al. 2014. Colon cancer cells escape 5FU chemotherapy–induced cell death by entering stemness and quiescence associated with the c-Yes/YAP axis. Clin. Cancer Res. 20:837–46 [Google Scholar]
  184. Wierzbicki PM, Adrych K, Kartanowicz D, Stanislawowski M, Kowalczyk A. 184.  et al. 2013. Underexpression of LATS1 TSG in colorectal cancer is associated with promoter hypermethylation. World J. Gastroenterol. 19:4363–73 [Google Scholar]
  185. Konsavage WM Jr, Kyler SL, Rennoll SA, Jin G, Yochum GS. 185.  2012. Wnt/β-catenin signaling regulates Yes-associated protein (YAP) gene expression in colorectal carcinoma cells. J. Biol. Chem. 287:11730–39 [Google Scholar]
  186. Shih HP, Wang A, Sander M. 186.  2013. Pancreas organogenesis: from lineage determination to morphogenesis. Annu. Rev. Cell Dev. Biol. 29:81–105 [Google Scholar]
  187. Gao T, Zhou D, Yang C, Singh T, Penzo-Mendez A. 187.  et al. 2013. Hippo signaling regulates differentiation and maintenance in the exocrine pancreas. Gastroenterology 144:1543–53 [Google Scholar]
  188. George NM, Day CE, Boerner BP, Johnson RL, Sarvetnick NE. 188.  2012. Hippo signaling regulates pancreas development through inactivation of Yap. Mol. Cell. Biol. 32:5116–28 [Google Scholar]
  189. Hariharan D, Saied A, Kocher HM. 189.  2008. Analysis of mortality rates for pancreatic cancer across the world. HPB 10:58–62 [Google Scholar]
  190. Diep CH, Zucker KM, Hostetter G, Watanabe A, Hu C. 190.  et al. 2012. Down-regulation of Yes Associated Protein 1 expression reduces cell proliferation and clonogenicity of pancreatic cancer cells. PLOS ONE 7:e32783 [Google Scholar]
  191. Zhang W, Nandakumar N, Shi Y, Manzano M, Smith A. 191.  et al. 2014. Downstream of mutant KRAS, the transcription regulator YAP is essential for neoplastic progression to pancreatic ductal adenocarcinoma. Sci. Signal. 7:ra42 [Google Scholar]
  192. Enger TB, Samad-Zadeh A, Bouchie MP, Skarstein K, Galtung HK. 192.  et al. 2013. The Hippo signaling pathway is required for salivary gland development and its dysregulation is associated with Sjogren's syndrome. Lab. Investig. 93:1203–18 [Google Scholar]
  193. Tumaneng K, Schlegelmilch K, Russell RC, Yimlamai D, Basnet H. 193.  et al. 2012. YAP mediates crosstalk between the Hippo and PI(3)K-TOR pathways by suppressing PTEN via miR-29. Nat. Cell Biol. 14:1322–29 [Google Scholar]
  194. Lam-Himlin DM, Daniels JA, Gayyed MF, Dong J, Maitra A. 194.  et al. 2006. The Hippo pathway in human upper gastrointestinal dysplasia and carcinoma: a novel oncogenic pathway. Int. J. Gastrointest. Cancer 37:103–9 [Google Scholar]
  195. Yeo MK, Kim SH, Kim JM, Huang SM, Kim MR. 195.  et al. 2012. Correlation of expression of phosphorylated and non-phosphorylated Yes-associated protein with clinicopathological parameters in esophageal squamous cell carcinoma in a Korean population. Anticancer Res. 32:3835–40 [Google Scholar]
  196. Muramatsu T, Imoto I, Matsui T, Kozaki K, Haruki S. 196.  et al. 2011. YAP is a candidate oncogene for esophageal squamous cell carcinoma. Carcinogenesis 32:389–98 [Google Scholar]
  197. Kakiuchi M, Nishizawa T, Ueda H, Gotoh K, Tanaka A. 197.  et al. 2014. Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma. Nat. Genet. 46:583–87 [Google Scholar]
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Hippo Pathway Regulation of Gastrointestinal Tissues
Annual Review of Physiology 77, 201 (2015); https://doi.org/10.1146/annurev-physiol-021014-071733
/content/journals/10.1146/annurev-physiol-021014-071733
/content/journals/10.1146/annurev-physiol-021014-071733
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