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PMID: 20951342 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review

The hippo signaling pathway in development and cancer.

Developmental cell ·Vol. 19 ·No. 4 ·2010-10-19 ·Pages 491-505

Pan D

Abstract

First discovered in Drosophila, the Hippo signaling pathway is a conserved regulator of organ size. Central to this pathway is a kinase cascade leading from the tumor suppressor Hippo (Mst1 and Mst2 in mammals) to the oncoprotein Yki (YAP and TAZ in mammals), a transcriptional coactivator of target genes involved in cell proliferation and survival. Here, I review recent progress in elucidating the molecular mechanism and physiological function of Hippo signaling in Drosophila and mammals. These studies suggest that the core Hippo kinase cascade integrates multiple upstream inputs, enabling dynamic regulation of tissue homeostasis in animal development and physiology.

MeSH Terms
Animals Drosophila Proteins/metabolism Drosophila melanogaster/metabolism Embryonic Development Gene Expression Regulation Humans Intracellular Signaling Peptides and Proteins/metabolism Neoplasms/genetics,metabolism,pathology Protein Serine-Threonine Kinases/metabolism Signal Transduction Tumor Suppressor Proteins/metabolism
Chemicals
Drosophila Proteins Intracellular Signaling Peptides and Proteins Tumor Suppressor Proteins Protein Serine-Threonine Kinases hpo protein, Drosophila
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Pan Duojia
Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. [email protected]
References (181)
181 references, click to expand
  1. A novel TEAD1 mutation is the causative allele in Sveinsson's chorioretinal atrophy (helicoid peripapillary chorioretinal degeneration).
    Hum Mol Genet. 2004 May 1;13(9):975-81 PMID: 15016762
  2. The apical-basal cell polarity determinant Crumbs regulates Hippo signaling in Drosophila.
    Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15810-5 PMID: 20798049
  3. 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. 2006 Sep;273(18):4264-76 PMID: 16930133
  4. Combined functional genomic and proteomic approaches identify a PP2A complex as a negative regulator of Hippo signaling.
    Mol Cell. 2010 Aug 27;39(4):521-34 PMID: 20797625
  5. The transcriptional co-activator TAZ interacts differentially with transcriptional enhancer factor-1 (TEF-1) family members.
    Biochem J. 2005 May 15;388(Pt 1):217-25 PMID: 15628970
  6. Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12).
    Nat Genet. 1999 Oct;23(2):217-21 PMID: 10508521
  7. Hippo pathway-dependent and -independent roles of RASSF6.
    Sci Signal. 2009 Sep 29;2(90):ra59 PMID: 19797269
  8. The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis.
    Nat Cell Biol. 2006 Jan;8(1):27-36 PMID: 16341207
  9. Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway.
    Nat Cell Biol. 2003 Oct;5(10):914-20 PMID: 14502294
  10. crumbs encodes an EGF-like protein expressed on apical membranes of Drosophila epithelial cells and required for organization of epithelia.
    Cell. 1990 Jun 1;61(5):787-99 PMID: 2344615
  11. The Salvador partner Hippo promotes apoptosis and cell-cycle exit in Drosophila.
    Nat Cell Biol. 2003 Oct;5(10):921-7 PMID: 14502295
  12. The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1.
    Oncogene. 2005 Mar 17;24(12):2076-86 PMID: 15688006
  13. Rare amplicons implicate frequent deregulation of cell fate specification pathways in oral squamous cell carcinoma.
    Oncogene. 2005 Jun 16;24(26):4232-42 PMID: 15824737
  14. The FERM-domain protein Expanded regulates Hippo pathway activity via direct interactions with the transcriptional activator Yorkie.
    Dev Cell. 2009 Mar;16(3):411-20 PMID: 19289086
  15. A comprehensive search for DNA amplification in lung cancer identifies inhibitors of apoptosis cIAP1 and cIAP2 as candidate oncogenes.
    Hum Mol Genet. 2003 Apr 1;12(7):791-801 PMID: 12651874
  16. Identification of cIAP1 as a candidate target gene within an amplicon at 11q22 in esophageal squamous cell carcinomas.
    Cancer Res. 2001 Sep 15;61(18):6629-34 PMID: 11559525
  17. TEADs mediate nuclear retention of TAZ to promote oncogenic transformation.
    J Biol Chem. 2009 May 22;284(21):14347-58 PMID: 19324876
  18. The apical transmembrane protein Crumbs functions as a tumor suppressor that regulates Hippo signaling by binding to Expanded.
    Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10532-7 PMID: 20498073
  19. The fat cadherin acts through the hippo tumor-suppressor pathway to regulate tissue size.
    Curr Biol. 2006 Nov 7;16(21):2090-100 PMID: 16996265
  20. Redundant roles of Tead1 and Tead2 in notochord development and the regulation of cell proliferation and survival.
    Mol Cell Biol. 2008 May;28(10):3177-89 PMID: 18332127
  21. Nonautonomous planar polarity patterning in Drosophila: dishevelled-independent functions of frizzled.
    Dev Cell. 2002 Dec;3(6):851-63 PMID: 12479810
  22. A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors.
    Cell. 2006 Mar 24;124(6):1169-81 PMID: 16564011
  23. TAZ, a transcriptional modulator of mesenchymal stem cell differentiation.
    Science. 2005 Aug 12;309(5737):1074-8 PMID: 16099986
  24. Structural and functional analysis of the YAP-binding domain of human TEAD2.
    Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7293-8 PMID: 20368466
  25. Structural basis of YAP recognition by TEAD4 in the hippo pathway.
    Genes Dev. 2010 Feb 1;24(3):290-300 PMID: 20123908
  26. Structural insights into the YAP and TEAD complex.
    Genes Dev. 2010 Feb 1;24(3):235-40 PMID: 20123905
  27. 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. 1995 Mar 1;9(5):534-46 PMID: 7698644
  28. TAZ interacts with TTF-1 and regulates expression of surfactant protein-C.
    J Biol Chem. 2004 Apr 23;279(17):17384-90 PMID: 14970209
  29. Transcriptional coactivation of bone-specific transcription factor Cbfa1 by TAZ.
    Mol Cell Biol. 2003 Feb;23(3):1004-13 PMID: 12529404
  30. Role of the polarity determinant crumbs in suppressing mammalian epithelial tumor progression.
    Cancer Res. 2008 Jun 1;68(11):4105-15 PMID: 18519669
  31. The tumor-suppressor gene fat controls tissue growth upstream of expanded in the hippo signaling pathway.
    Curr Biol. 2006 Nov 7;16(21):2081-9 PMID: 16996266
  32. Mob as tumor suppressor is activated by Hippo kinase for growth inhibition in Drosophila.
    EMBO J. 2007 Apr 4;26(7):1772-81 PMID: 17347649
  33. Hippo signaling regulates Yorkie nuclear localization and activity through 14-3-3 dependent and independent mechanisms.
    Dev Biol. 2010 Jan 15;337(2):303-12 PMID: 19900439
  34. Transcription factor choice in the Hippo signaling pathway: homothorax and yorkie regulation of the microRNA bantam in the progenitor domain of the Drosophila eye imaginal disc.
    Genes Dev. 2009 Oct 1;23(19):2307-19 PMID: 19762509
  35. TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition.
    J Biol Chem. 2009 May 15;284(20):13355-13362 PMID: 19324877
  36. A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt-Oram syndrome.
    Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18034-9 PMID: 16332960
  37. Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase.
    Cell. 2003 May 16;113(4):507-17 PMID: 12757711
  38. Integrated profiling of basal and luminal breast cancers.
    Cancer Res. 2007 Dec 15;67(24):11565-75 PMID: 18089785
  39. The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass.
    Dev Cell. 2009 Mar;16(3):398-410 PMID: 19289085
  40. The Hippo pathway regulates the bantam microRNA to control cell proliferation and apoptosis in Drosophila.
    Cell. 2006 Aug 25;126(4):767-74 PMID: 16923395
  41. Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase.
    Development. 1995 Apr;121(4):1053-63 PMID: 7743921
  42. Delineation of a Fat tumor suppressor pathway.
    Nat Genet. 2006 Oct;38(10):1142-50 PMID: 16980976
  43. Both phosphorylation and caspase-mediated cleavage contribute to regulation of the Ste20-like protein kinase Mst1 during CD95/Fas-induced apoptosis.
    J Biol Chem. 2001 May 4;276(18):14909-15 PMID: 11278782
  44. Physical interaction with Yes-associated protein enhances p73 transcriptional activity.
    J Biol Chem. 2001 May 4;276(18):15164-73 PMID: 11278685
  45. Boundaries of Dachsous Cadherin activity modulate the Hippo signaling pathway to induce cell proliferation.
    Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):14897-902 PMID: 18809931
  46. The tumor suppressor genes dachsous and fat modulate different signalling pathways by regulating dally and dally-like.
    Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9645-50 PMID: 18621676
  47. Liver regeneration.
    Science. 1997 Apr 4;276(5309):60-6 PMID: 9082986
  48. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor.
    Cell. 1993 Mar 12;72(5):791-800 PMID: 8453669
  49. Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras.
    Biochem J. 2004 Jul 15;381(Pt 2):453-62 PMID: 15109305
  50. The LIM protein Ajuba is recruited to cadherin-dependent cell junctions through an association with alpha-catenin.
    J Biol Chem. 2003 Jan 10;278(2):1220-8 PMID: 12417594
  51. Prognostic significance of mammalian sterile20-like kinase 1 in colorectal cancer.
    Mod Pathol. 2007 Mar;20(3):331-8 PMID: 17277767
  52. Hippo signaling in organ size control.
    Genes Dev. 2007 Apr 15;21(8):886-97 PMID: 17437995
  53. Mapping of MST1 kinase sites of phosphorylation. Activation and autophosphorylation.
    J Biol Chem. 2002 Nov 8;277(45):42987-96 PMID: 12223493
  54. Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression.
    Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1431-6 PMID: 20080598
  55. Expanded functions in the apical cell domain to regulate the growth rate of imaginal discs.
    Dev Genet. 1997;20(2):103-10 PMID: 9144921
  56. TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal.
    Nat Cell Biol. 2008 Jul;10(7):837-48 PMID: 18568018
  57. Processing and phosphorylation of the Fat receptor.
    Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):11989-94 PMID: 19574458
  58. The neurofibromatosis-2 homologue, Merlin, and the tumor suppressor expanded function together in Drosophila to regulate cell proliferation and differentiation.
    Development. 2000 Mar;127(6):1315-24 PMID: 10683183
  59. The Hippo-Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis.
    Proc Natl Acad Sci U S A. 2010 May 4;107(18):8248-53 PMID: 20404163
  60. Shar-pei mediates cell proliferation arrest during imaginal disc growth in Drosophila.
    Development. 2002 Dec;129(24):5719-30 PMID: 12421711
  61. Tumor suppressor LATS1 is a negative regulator of oncogene YAP.
    J Biol Chem. 2008 Feb 29;283(9):5496-509 PMID: 18158288
  62. Phosphorylation and dimerization regulate nucleocytoplasmic shuttling of mammalian STE20-like kinase (MST).
    J Biol Chem. 2002 Apr 5;277(14):12351-8 PMID: 11805089
  63. TEAD/TEF transcription factors utilize the activation domain of YAP65, a Src/Yes-associated protein localized in the cytoplasm.
    Genes Dev. 2001 May 15;15(10):1229-41 PMID: 11358867
  64. Lgl, aPKC, and Crumbs regulate the Salvador/Warts/Hippo pathway through two distinct mechanisms.
    Curr Biol. 2010 Apr 13;20(7):573-81 PMID: 20362447
  65. A Sveinsson's chorioretinal atrophy-associated missense mutation in mouse Tead1 affects its interaction with the co-factors YAP and TAZ.
    Biochem Biophys Res Commun. 2007 Oct 5;361(4):1022-6 PMID: 17689488
  66. Down-regulation of LATS1 and LATS2 mRNA expression by promoter hypermethylation and its association with biologically aggressive phenotype in human breast cancers.
    Clin Cancer Res. 2005 Feb 15;11(4):1380-5 PMID: 15746036
  67. RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1.
    Nat Immunol. 2003 Aug;4(8):741-8 PMID: 12845325
  68. Membrane organization and tumorigenesis--the NF2 tumor suppressor, Merlin.
    Genes Dev. 2005 Oct 1;19(19):2265-77 PMID: 16204178
  69. Akt phosphorylates the Yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis.
    Mol Cell. 2003 Jan;11(1):11-23 PMID: 12535517
  70. NDR kinase is activated by RASSF1A/MST1 in response to Fas receptor stimulation and promotes apoptosis.
    Curr Biol. 2008 Dec 9;18(23):1889-95 PMID: 19062280
  71. The MST1 and hMOB1 tumor suppressors control human centrosome duplication by regulating NDR kinase phosphorylation.
    Curr Biol. 2009 Nov 3;19(20):1692-702 PMID: 19836237
  72. RASSF1A is part of a complex similar to the Drosophila Hippo/Salvador/Lats tumor-suppressor network.
    Curr Biol. 2007 Apr 17;17(8):700-5 PMID: 17379520
  73. Promoter hypermethylation-mediated down-regulation of LATS1 and LATS2 in human astrocytoma.
    Neurosci Res. 2006 Dec;56(4):450-8 PMID: 17049657
  74. Frequent hypermethylation of MST1 and MST2 in soft tissue sarcoma.
    Mol Carcinog. 2007 Oct;46(10):865-71 PMID: 17538946
  75. Intrinsic and extrinsic control of growth in developing organs.
    Q Rev Biol. 1984 Dec;59(4):387-415 PMID: 6393189
  76. Human LATS1 is a mitotic exit network kinase.
    Cancer Res. 2005 Aug 1;65(15):6568-75 PMID: 16061636
  77. Discs Lost, a novel multi-PDZ domain protein, establishes and maintains epithelial polarity.
    Cell. 1999 Mar 19;96(6):833-45 PMID: 10102271
  78. Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1.
    EMBO J. 1998 Apr 15;17(8):2224-34 PMID: 9545236
  79. Yes-associated protein is an independent prognostic marker in hepatocellular carcinoma.
    Cancer. 2009 Oct 1;115(19):4576-85 PMID: 19551889
  80. Fat cadherin modulates organ size in Drosophila via the Salvador/Warts/Hippo signaling pathway.
    Curr Biol. 2006 Nov 7;16(21):2101-10 PMID: 17045801
  81. Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon.
    Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12405-10 PMID: 16894141
  82. Developmental compartments and planar polarity in Drosophila.
    Curr Biol. 2002 Jul 23;12(14):1189-98 PMID: 12176328
  83. Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver.
    Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1437-42 PMID: 20080689
  84. A human homolog of Drosophila warts tumor suppressor, h-warts, localized to mitotic apparatus and specifically phosphorylated during mitosis.
    FEBS Lett. 1999 Oct 8;459(2):159-65 PMID: 10518011
  85. Mst2 and Lats kinases regulate apoptotic function of Yes kinase-associated protein (YAP).
    J Biol Chem. 2008 Oct 10;283(41):27534-27546 PMID: 18640976
  86. Rassf family of tumor suppressor polypeptides.
    J Biol Chem. 2009 Apr 24;284(17):11001-5 PMID: 19091744
  87. Glomerulocystic kidney disease in mice with a targeted inactivation of Wwtr1.
    Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1631-6 PMID: 17251353
  88. Dachs: an unconventional myosin that functions downstream of Fat to regulate growth, affinity and gene expression in Drosophila.
    Development. 2006 Jul;133(13):2539-51 PMID: 16735478
  89. The RASSF proteins in cancer; from epigenetic silencing to functional characterization.
    Biochim Biophys Acta. 2009 Dec;1796(2):114-28 PMID: 19344752
  90. Defects in yolk sac vasculogenesis, chorioallantoic fusion, and embryonic axis elongation in mice with targeted disruption of Yap65.
    Mol Cell Biol. 2006 Jan;26(1):77-87 PMID: 16354681
  91. A role for TAZ in migration, invasion, and tumorigenesis of breast cancer cells.
    Cancer Res. 2008 Apr 15;68(8):2592-8 PMID: 18413727
  92. The salvador-warts-hippo pathway is required for epithelial proliferation and axis specification in Drosophila.
    Curr Biol. 2007 Nov 6;17(21):1871-8 PMID: 17964161
  93. Separating the adhesive and signaling functions of the Fat and Dachsous protocadherins.
    Development. 2006 Jun;133(12):2315-24 PMID: 16687445
  94. The pro-apoptotic kinase Mst1 and its caspase cleavage products are direct inhibitors of Akt1.
    EMBO J. 2007 Oct 31;26(21):4523-34 PMID: 17932490
  95. Array-based comparative genomic hybridization identifies localized DNA amplifications and homozygous deletions in pancreatic cancer.
    Neoplasia. 2005 Jun;7(6):556-62 PMID: 16036106
  96. The Drosophila tumor suppressors Expanded and Merlin differentially regulate cell cycle exit, apoptosis, and Wingless signaling.
    Dev Biol. 2007 Apr 1;304(1):102-15 PMID: 17258190
  97. Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2.
    Nature. 1993 Jun 10;363(6429):515-21 PMID: 8379998
  98. MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation.
    Curr Biol. 2008 Mar 11;18(5):311-21 PMID: 18328708
  99. The DeMSTification of mammalian Ste20 kinases.
    Curr Biol. 2009 May 26;19(10):R421-5 PMID: 19467213
  100. The DHHC palmitoyltransferase approximated regulates Fat signaling and Dachs localization and activity.
    Curr Biol. 2008 Sep 23;18(18):1390-5 PMID: 18804377
  101. Expanded and fat regulate growth and differentiation in the Drosophila eye through multiple signaling pathways.
    Dev Biol. 2007 May 1;305(1):187-201 PMID: 17359963
  102. Transcriptional activity of Pax3 is co-activated by TAZ.
    Biochem Biophys Res Commun. 2006 Jan 13;339(2):533-9 PMID: 16300735
  103. Drosophila Stardust is a partner of Crumbs in the control of epithelial cell polarity.
    Nature. 2001 Dec 6;414(6864):638-43 PMID: 11740560
  104. Modulation of fat:dachsous binding by the cadherin domain kinase four-jointed.
    Curr Biol. 2010 May 11;20(9):811-7 PMID: 20434335
  105. Drosophila Stardust interacts with Crumbs to control polarity of epithelia but not neuroblasts.
    Nature. 2001 Dec 6;414(6864):634-8 PMID: 11740559
  106. Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene.
    Cancer Cell. 2009 Nov 6;16(5):425-38 PMID: 19878874
  107. Influence of fat-hippo and notch signaling on the proliferation and differentiation of Drosophila optic neuroepithelia.
    Development. 2010 Jul;137(14):2397-408 PMID: 20570939
  108. Elucidation of a universal size-control mechanism in Drosophila and mammals.
    Cell. 2007 Sep 21;130(6):1120-33 PMID: 17889654
  109. A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP).
    Genes Dev. 2010 Jan 1;24(1):72-85 PMID: 20048001
  110. YAP regulates neural progenitor cell number via the TEA domain transcription factor.
    Genes Dev. 2008 Dec 1;22(23):3320-34 PMID: 19015275
  111. Clinical significance of the loss of MATS1 mRNA expression in colorectal cancer.
    Int J Oncol. 2007 Aug;31(2):333-8 PMID: 17611689
  112. Two separate molecular systems, Dachsous/Fat and Starry night/Frizzled, act independently to confer planar cell polarity.
    Development. 2006 Nov;133(22):4561-72 PMID: 17075008
  113. Akt phosphorylates MstI and prevents its proteolytic activation, blocking FOXO3 phosphorylation and nuclear translocation.
    J Biol Chem. 2007 Oct 19;282(42):30836-44 PMID: 17726016
  114. Shedding light on Merlin's wizardry.
    Trends Cell Biol. 2007 May;17(5):222-9 PMID: 17442573
  115. Robustness of cellular functions.
    Cell. 2004 Sep 17;118(6):675-85 PMID: 15369668
  116. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control.
    Genes Dev. 2007 Nov 1;21(21):2747-61 PMID: 17974916
  117. Four-jointed modulates growth and planar polarity by reducing the affinity of dachsous for fat.
    Curr Biol. 2010 May 11;20(9):803-10 PMID: 20434337
  118. The TEAD/TEF family of transcription factor Scalloped mediates Hippo signaling in organ size control.
    Dev Cell. 2008 Mar;14(3):377-87 PMID: 18258485
  119. Ajuba LIM proteins are negative regulators of the Hippo signaling pathway.
    Curr Biol. 2010 Apr 13;20(7):657-62 PMID: 20303269
  120. Identification of Nore1 as a potential Ras effector.
    J Biol Chem. 1998 Mar 6;273(10):5439-42 PMID: 9488663
  121. Salvador-warts-hippo signaling promotes Drosophila posterior follicle cell maturation downstream of notch.
    Curr Biol. 2007 Nov 6;17(21):1864-70 PMID: 17964162
  122. hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts.
    Cell. 2003 Aug 22;114(4):445-56 PMID: 12941273
  123. In vivo analysis of Yorkie phosphorylation sites.
    Oncogene. 2009 Apr 30;28(17):1916-27 PMID: 19330023
  124. TEAD mediates YAP-dependent gene induction and growth control.
    Genes Dev. 2008 Jul 15;22(14):1962-71 PMID: 18579750
  125. The TEAD/TEF family protein Scalloped mediates transcriptional output of the Hippo growth-regulatory pathway.
    Dev Cell. 2008 Mar;14(3):388-98 PMID: 18258486
  126. A matter of life and death.
    Cancer Cell. 2002 Feb;1(1):19-30 PMID: 12086884
  127. Regulation of Frizzled by fat-like cadherins during planar polarity signaling in the Drosophila compound eye.
    Cell. 2002 Mar 8;108(5):675-88 PMID: 11893338
  128. YAP1 is amplified and up-regulated in hedgehog-associated medulloblastomas and mediates Sonic hedgehog-driven neural precursor proliferation.
    Genes Dev. 2009 Dec 1;23(23):2729-41 PMID: 19952108
  129. The WW domain protein Kibra acts upstream of Hippo in Drosophila.
    Dev Cell. 2010 Feb 16;18(2):309-16 PMID: 20159600
  130. The growth regulators warts/lats and melted interact in a bistable loop to specify opposite fates in Drosophila R8 photoreceptors.
    Cell. 2005 Sep 9;122(5):775-87 PMID: 16143107
  131. In vivo regulation of Yorkie phosphorylation and localization.
    Development. 2008 Mar;135(6):1081-8 PMID: 18256197
  132. Yap is a novel regulator of C2C12 myogenesis.
    Biochem Biophys Res Commun. 2010 Mar 19;393(4):619-24 PMID: 20153295
  133. Phosphorylation-independent repression of Yorkie in Fat-Hippo signaling.
    Dev Biol. 2009 Nov 1;335(1):188-97 PMID: 19733165
  134. Kibra functions as a tumor suppressor protein that regulates Hippo signaling in conjunction with Merlin and Expanded.
    Dev Cell. 2010 Feb 16;18(2):288-99 PMID: 20159598
  135. A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span.
    Cell. 2006 Jun 2;125(5):987-1001 PMID: 16751106
  136. Mob as tumor suppressor is activated at the cell membrane to control tissue growth and organ size in Drosophila.
    Dev Biol. 2010 Jan 15;337(2):274-83 PMID: 19913529
  137. RASSF1A elicits apoptosis through an MST2 pathway directing proapoptotic transcription by the p73 tumor suppressor protein.
    Mol Cell. 2007 Sep 21;27(6):962-75 PMID: 17889669
  138. Phosphorylation of the tumor suppressor fat is regulated by its ligand Dachsous and the kinase discs overgrown.
    Curr Biol. 2009 Jul 14;19(13):1112-7 PMID: 19540118
  139. Crumbs regulates Salvador/Warts/Hippo signaling in Drosophila via the FERM-domain protein Expanded.
    Curr Biol. 2010 Apr 13;20(7):582-90 PMID: 20362445
  140. TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway.
    Mol Cell Biol. 2008 Apr;28(7):2426-36 PMID: 18227151
  141. Expression of Yes-associated protein in common solid tumors.
    Hum Pathol. 2008 Nov;39(11):1582-9 PMID: 18703216
  142. The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP.
    Cell. 2005 Aug 12;122(3):421-34 PMID: 16096061
  143. Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus.
    Cell. 2010 Feb 19;140(4):477-90 PMID: 20178741
  144. Kibra is a regulator of the Salvador/Warts/Hippo signaling network.
    Dev Cell. 2010 Feb 16;18(2):300-8 PMID: 20159599
  145. DNA profiling of primary serous ovarian and fallopian tube carcinomas with array comparative genomic hybridization and multiplex ligation-dependent probe amplification.
    J Pathol. 2007 Sep;213(1):46-55 PMID: 17668415
  146. A WW domain-containing yes-associated protein (YAP) is a novel transcriptional co-activator.
    EMBO J. 1999 May 4;18(9):2551-62 PMID: 10228168
  147. YAP-dependent induction of amphiregulin identifies a non-cell-autonomous component of the Hippo pathway.
    Nat Cell Biol. 2009 Dec;11(12):1444-50 PMID: 19935651
  148. Mammalian Tead proteins regulate cell proliferation and contact inhibition as transcriptional mediators of Hippo signaling.
    Development. 2008 Dec;135(24):4059-69 PMID: 19004856
  149. The Drosophila Ste20 family kinase dMST functions as a tumor suppressor by restricting cell proliferation and promoting apoptosis.
    Genes Dev. 2003 Oct 15;17(20):2514-9 PMID: 14561774
  150. SCALLOPED interacts with YORKIE, the nuclear effector of the hippo tumor-suppressor pathway in Drosophila.
    Curr Biol. 2008 Mar 25;18(6):435-41 PMID: 18313299
  151. The Hippo pathway regulates Wnt/beta-catenin signaling.
    Dev Cell. 2010 Apr 20;18(4):579-91 PMID: 20412773
  152. Identification of Fat4 as a candidate tumor suppressor gene in breast cancers.
    Int J Cancer. 2009 Feb 15;124(4):793-8 PMID: 19048595
  153. The Drosophila RASSF homolog antagonizes the hippo pathway.
    Curr Biol. 2006 Dec 19;16(24):2459-65 PMID: 17174922
  154. Morphogen control of wing growth through the Fat signaling pathway.
    Dev Cell. 2008 Aug;15(2):309-21 PMID: 18694569
  155. salvador Promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines.
    Cell. 2002 Aug 23;110(4):467-78 PMID: 12202036
  156. Fat and expanded act in parallel to regulate growth through warts.
    Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20362-7 PMID: 18077345
  157. The Hippo pathway regulates apical-domain size independently of its growth-control function.
    J Cell Sci. 2009 Jul 15;122(Pt 14):2360-70 PMID: 19531586
  158. Control of cell proliferation and apoptosis by mob as tumor suppressor, mats.
    Cell. 2005 Mar 11;120(5):675-85 PMID: 15766530
  159. Novel genomic aberrations in testicular germ cell tumors by array-CGH, and associated gene expression changes.
    Cell Oncol. 2006;28(5-6):315-26 PMID: 17167184
  160. The hippo pathway promotes Notch signaling in regulation of cell differentiation, proliferation, and oocyte polarity.
    PLoS One. 2008 Mar 12;3(3):e1761 PMID: 18335037
  161. A crucial role of WW45 in developing epithelial tissues in the mouse.
    EMBO J. 2008 Apr 23;27(8):1231-42 PMID: 18369314
  162. The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis.
    Cell. 2003 Aug 22;114(4):457-67 PMID: 12941274
  163. Nf2/Merlin controls progenitor homeostasis and tumorigenesis in the liver.
    Genes Dev. 2010 Aug 15;24(16):1718-30 PMID: 20675406
  164. Crumbs proteins in epithelial morphogenesis.
    Front Biosci (Landmark Ed). 2009 Jan 01;14:2149-69 PMID: 19273190
  165. The tumour suppressor Hippo acts with the NDR kinases in dendritic tiling and maintenance.
    Nature. 2006 Sep 14;443(7108):210-3 PMID: 16906135
  166. TAZ promotes PC2 degradation through a SCFbeta-Trcp E3 ligase complex.
    Mol Cell Biol. 2007 Sep;27(18):6383-95 PMID: 17636028
  167. Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta pathways.
    Cell. 2009 Nov 13;139(4):757-69 PMID: 19914168
  168. The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44.
    Genes Dev. 2001 Apr 15;15(8):968-80 PMID: 11316791
  169. Loss of Fat4 disrupts PCP signaling and oriented cell division and leads to cystic kidney disease.
    Nat Genet. 2008 Aug;40(8):1010-5 PMID: 18604206
  170. Yes-associated protein (YAP) functions as a tumor suppressor in breast.
    Cell Death Differ. 2008 Nov;15(11):1752-9 PMID: 18617895
  171. YAP1 increases organ size and expands undifferentiated progenitor cells.
    Curr Biol. 2007 Dec 4;17(23):2054-60 PMID: 17980593
  172. Drosophila lowfat, a novel modulator of Fat signaling.
    Development. 2009 Oct;136(19):3223-33 PMID: 19710173
  173. Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach.
    Cell. 2006 Jun 30;125(7):1253-67 PMID: 16814713
  174. Regulation of gene expression at the beginning of mammalian development and the TEAD family of transcription factors.
    Dev Genet. 1998;22(1):43-55 PMID: 9499579
  175. Differential requirement of Salvador-Warts-Hippo pathway members for organ size control in Drosophila melanogaster.
    Development. 2010 Mar;137(5):735-43 PMID: 20110315
  176. Four-jointed is a Golgi kinase that phosphorylates a subset of cadherin domains.
    Science. 2008 Jul 18;321(5887):401-4 PMID: 18635802
  177. The bantam microRNA is a target of the hippo tumor-suppressor pathway.
    Curr Biol. 2006 Oct 10;16(19):1895-904 PMID: 16949821
  178. The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals.
    Dev Cell. 2010 Jul 20;19(1):27-38 PMID: 20643348
  179. From cell structure to transcription: Hippo forges a new path.
    Cell. 2006 Jan 27;124(2):267-73 PMID: 16439203
  180. Human MOB1 expression in non-small-cell lung cancer.
    Clin Lung Cancer. 2007 Jan;8(4):273-6 PMID: 17311693
  181. Multiple renal cysts, urinary concentration defects, and pulmonary emphysematous changes in mice lacking TAZ.
    Am J Physiol Renal Physiol. 2008 Mar;294(3):F542-53 PMID: 18172001
Article Info
Journal
Developmental cell
Abbr.
Dev Cell
ISSN
1878-1551
DOI
10.1016/j.devcel.2010.09.011
Email
[email protected]
Published
2010-10-19
Pages
491-505
Language
English
Region
United States
NLM ID
101120028
PMCID
PMC3124840
Subset
IM
Grants
Howard Hughes Medical Institute · United States
NEI NIH HHS · R01 EY015708 · United States
NEI NIH HHS · EY015708 · United States
External Links
PubMed source DOI: 10.1016/j.devcel.2010.09.011 PMC Full Text View journal details
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