The hippo signaling pathway in development and cancer.

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.

[1]  S. Blair,et al.  Separating the adhesive and signaling functions of the Fat and Dachsous protocadherins , 2006, Development.

[2]  N. Tapon,et al.  The Salvador partner Hippo promotes apoptosis and cell-cycle exit in Drosophila , 2003, Nature Cell Biology.

[3]  Judit Villén,et al.  A Conserved MST-FOXO Signaling Pathway Mediates Oxidative-Stress Responses and Extends Life Span , 2006, Cell.

[4]  Michinori Kitagawa.  A Sveinsson's chorioretinal atrophy-associated missense mutation in mouse Tead1 affects its interaction with the co-factors YAP and TAZ. , 2007, Biochemical and biophysical research communications.

[5]  M. Yaffe,et al.  TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal , 2008, Nature Cell Biology.

[6]  Jianmin Zhang,et al.  YAP-dependent induction of amphiregulin identifies a non-cell-autonomous component of the Hippo pathway , 2009, Nature Cell Biology.

[7]  B. Wang,et al.  The TEAD/TEF family of transcription factor Scalloped mediates Hippo signaling in organ size control. , 2008, Developmental cell.

[8]  Lin-Feng Chen,et al.  A WW domain‐containing Yes‐associated protein (YAP) is a novel transcriptional co‐activator , 1999, The EMBO journal.

[9]  R. Fehon,et al.  The neurofibromatosis-2 homologue, Merlin, and the tumor suppressor expanded function together in Drosophila to regulate cell proliferation and differentiation. , 2000, Development.

[10]  H. Sasaki,et al.  Human MOB1 expression in non-small-cell lung cancer. , 2007, Clinical lung cancer.

[11]  W. Deng,et al.  Kibra functions as a tumor suppressor protein that regulates Hippo signaling in conjunction with Merlin and Expanded. , 2010, Developmental cell.

[12]  H. Stefánsson,et al.  A novel TEAD1 mutation is the causative allele in Sveinsson's chorioretinal atrophy (helicoid peripapillary chorioretinal degeneration). , 2004, Human molecular genetics.

[13]  Li Li,et al.  Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. , 2007, Genes & development.

[14]  Jianbin Huang,et al.  The Hippo Signaling Pathway Coordinately Regulates Cell Proliferation and Apoptosis by Inactivating Yorkie, the Drosophila Homolog of YAP , 2005, Cell.

[15]  Peter A Lawrence,et al.  Two separate molecular systems, Dachsous/Fat and Starry night/Frizzled, act independently to confer planar cell polarity , 2006, Development.

[16]  J. Inazawa,et al.  Identification of cIAP1 as a candidate target gene within an amplicon at 11q22 in esophageal squamous cell carcinomas. , 2001, Cancer research.

[17]  P. Yelick,et al.  The pro‐apoptotic kinase Mst1 and its caspase cleavage products are direct inhibitors of Akt1 , 2007, The EMBO journal.

[18]  Jay Z. Parrish,et al.  The tumour suppressor Hippo acts with the NDR kinases in dendritic tiling and maintenance , 2006, Nature.

[19]  L. Castagnoli,et al.  Physical Interaction with Yes-associated Protein Enhances p73 Transcriptional Activity* , 2001, The Journal of Biological Chemistry.

[20]  G. Michalopoulos,et al.  Liver Regeneration , 1997, Science.

[21]  Manfred Gessler,et al.  Loss of Fat4 disrupts PCP signaling and oriented cell division and leads to cystic kidney disease , 2008, Nature Genetics.

[22]  Peter W. Andrews,et al.  Novel Genomic Aberrations in Testicular Germ Cell Tumors by Array-CGH, and Associated Gene Expression Changes , 2006, Cellular oncology : the official journal of the International Society for Cellular Oncology.

[23]  K. Irvine,et al.  Four-jointed Is a Golgi Kinase That Phosphorylates a Subset of Cadherin Domains , 2008, Science.

[24]  N. Tapon,et al.  The Tumor-Suppressor Gene fat Controls Tissue Growth Upstream of Expanded in the Hippo Signaling Pathway , 2006, Current Biology.

[25]  S. Blair,et al.  The DHHC Palmitoyltransferase Approximated Regulates Fat Signaling and Dachs Localization and Activity , 2008, Current Biology.

[26]  Ilan Davis,et al.  The Salvador-Warts-Hippo Pathway Is Required for Epithelial Proliferation and Axis Specification in Drosophila , 2007, Current Biology.

[27]  K. Harvey,et al.  Fat Cadherin Modulates Organ Size in Drosophila via the Salvador/Warts/Hippo Signaling Pathway , 2006, Current Biology.

[28]  R. Xavier,et al.  Rassf Family of Tumor Suppressor Polypeptides* , 2009, Journal of Biological Chemistry.

[29]  Jonathan A. Cooper,et al.  Merlin/NF2 Suppresses Tumorigenesis by Inhibiting the E3 Ubiquitin Ligase CRL4DCAF1 in the Nucleus , 2010, Cell.

[30]  K. Makino,et al.  A human homolog of Drosophila warts tumor suppressor, h‐warts, localized to mitotic apparatus and specifically phosphorylated during mitosis , 1999, FEBS letters.

[31]  Wei-Guo Zhu,et al.  A comprehensive search for DNA amplification in lung cancer identifies inhibitors of apoptosis cIAP1 and cIAP2 as candidate oncogenes. , 2003, Human molecular genetics.

[32]  F. Gage,et al.  YAP regulates neural progenitor cell number via the TEA domain transcription factor. , 2008, Genes & development.

[33]  B. Thompson,et al.  Kibra Is a Regulator of the Salvador/Warts/Hippo Signaling Network , 2010, Developmental cell.

[34]  Jean S. Campbell,et al.  Liver regeneration. , 2012, Journal of hepatology.

[35]  Q. Zeng,et al.  A role for TAZ in migration, invasion, and tumorigenesis of breast cancer cells. , 2008, Cancer research.

[36]  L. Castagnoli,et al.  Physical interaction with Yes-associated protein enhances p73 transcriptional activity. , 2001, The Journal of biological chemistry.

[37]  I. Hariharan,et al.  The Drosophila Mst Ortholog, hippo, Restricts Growth and Cell Proliferation and Promotes Apoptosis , 2003, Cell.

[38]  E. Montgomery,et al.  Expression of Yes-associated protein in common solid tumors. , 2008, Human pathology.

[39]  T. Le Bihan,et al.  The FERM-domain protein Expanded regulates Hippo pathway activity via direct interactions with the transcriptional activator Yorkie. , 2009, Developmental cell.

[40]  U. Tepass,et al.  crumbs encodes an EGF-like protein expressed on apical membranes of Drosophila epithelial cells and required for organization of epithelia , 1990, Cell.

[41]  H. Bellen,et al.  Discs Lost, a Novel Multi-PDZ Domain Protein, Establishes and Maintains Epithelial Polarity , 2003, Cell.

[42]  N. Tapon,et al.  The Drosophila RASSF Homolog Antagonizes the Hippo Pathway , 2006, Current Biology.

[43]  David Strutt,et al.  Nonautonomous planar polarity patterning in Drosophila: dishevelled-independent functions of frizzled. , 2002, Developmental cell.

[44]  Shian Wu,et al.  The TEAD/TEF family protein Scalloped mediates transcriptional output of the Hippo growth-regulatory pathway. , 2008, Developmental cell.

[45]  J. Chernoff,et al.  The DeMSTification of Mammalian Ste20 Kinases , 2009, Current Biology.

[46]  K. Irvine,et al.  Processing and phosphorylation of the Fat receptor , 2009, Proceedings of the National Academy of Sciences.

[47]  Zhengyu Zha,et al.  TEAD Transcription Factors Mediate the Function of TAZ in Cell Growth and Epithelial-Mesenchymal Transition* , 2009, Journal of Biological Chemistry.

[48]  K. Harvey,et al.  Lgl, aPKC, and Crumbs Regulate the Salvador/Warts/Hippo Pathway through Two Distinct Mechanisms , 2010, Current Biology.

[49]  D. Pan,et al.  Hippo signaling in organ size control. , 2007, Genes & development.

[50]  Misa Nishikawa,et al.  Hippo Pathway–Dependent and –Independent Roles of RASSF6 , 2009, Science Signaling.

[51]  E. Krebs,et al.  Caspase‐mediated activation and induction of apoptosis by the mammalian Ste20‐like kinase Mst1 , 1998, The EMBO journal.

[52]  Shian Wu,et al.  hippo Encodes a Ste-20 Family Protein Kinase that Restricts Cell Proliferation and Promotes Apoptosis in Conjunction with salvador and warts , 2003, Cell.

[53]  P. Lawrence,et al.  Developmental Compartments and Planar Polarity in Drosophila , 2002, Current Biology.

[54]  Jeffrey D. Axelrod,et al.  Regulation of Frizzled by Fat-like Cadherins during Planar Polarity Signaling in the Drosophila Compound Eye , 2002, Cell.

[55]  Y. Uchijima,et al.  Transcriptional activity of Pax3 is co-activated by TAZ. , 2006, Biochemical and biophysical research communications.

[56]  E. Olson,et al.  A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt-Oram syndrome. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[57]  Juan Huang,et al.  Crumbs Regulates Salvador/Warts/Hippo Signaling in Drosophila via the FERM-Domain Protein Expanded , 2010, Current Biology.

[58]  Walter Kolch,et al.  RASSF1A elicits apoptosis through an MST2 pathway directing proapoptotic transcription by the p73 tumor suppressor protein. , 2007, Molecular cell.

[59]  Martina Schneider,et al.  Drosophila Stardust is a partner of Crumbs in the control of epithelial cell polarity , 2001, Nature.

[60]  J. Haines,et al.  A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor , 1993, Cell.

[61]  T. Magnuson,et al.  Defects in Yolk Sac Vasculogenesis, Chorioallantoic Fusion, and Embryonic Axis Elongation in Mice with Targeted Disruption of Yap65 , 2006, Molecular and Cellular Biology.

[62]  G. Halder,et al.  The apical-basal cell polarity determinant Crumbs regulates Hippo signaling in Drosophila , 2010, Proceedings of the National Academy of Sciences.

[63]  S. Yonehara,et al.  Phosphorylation and Dimerization Regulate Nucleocytoplasmic Shuttling of Mammalian STE20-like Kinase (MST)* , 2002, The Journal of Biological Chemistry.

[64]  Ryan S. Udan,et al.  The Fat Cadherin Acts through the Hippo Tumor-Suppressor Pathway to Regulate Tissue Size , 2006, Current Biology.

[65]  I. Hariharan,et al.  The Drosophila tumor suppressors Expanded and Merlin differentially regulate cell cycle exit, apoptosis, and Wingless signaling. , 2007, Developmental biology.

[66]  M. Yaffe,et al.  The transcriptional co-activator TAZ interacts differentially with transcriptional enhancer factor-1 (TEF-1) family members. , 2005, The Biochemical journal.

[67]  Thomas Benjamin,et al.  TAZ, a Transcriptional Modulator of Mesenchymal Stem Cell Differentiation , 2005, Science.

[68]  Michael A. Simon,et al.  Modulation of Fat:Dachsous Binding by the Cadherin Domain Kinase Four-Jointed , 2010, Current Biology.

[69]  J. Avruch,et al.  MOBKL1A/MOBKL1B Phosphorylation by MST1 and MST2 Inhibits Cell Proliferation , 2008, Current Biology.

[70]  Jonathan Chernoff,et al.  Apoptotic Phosphorylation of Histone H2B Is Mediated by Mammalian Sterile Twenty Kinase , 2003, Cell.

[71]  P. Northcott,et al.  YAP1 is amplified and up-regulated in hedgehog-associated medulloblastomas and mediates Sonic hedgehog-driven neural precursor proliferation. , 2009, Genes & development.

[72]  M. Giovannini,et al.  Nf2/Merlin controls progenitor homeostasis and tumorigenesis in the liver. , 2010, Genes & development.

[73]  E. Nigg,et al.  The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1 , 2005, Oncogene.

[74]  C. Rauskolb,et al.  Influence of Fat-Hippo and Notch signaling on the proliferation and differentiation of Drosophila optic neuroepithelia , 2010, Development.

[75]  Y. Miyoshi,et al.  Down-Regulation of LATS1 and LATS2 mRNA Expression by Promoter Hypermethylation and Its Association with Biologically Aggressive Phenotype in Human Breast Cancers , 2005, Clinical Cancer Research.

[76]  J. Avruch,et al.  Regulation of the MST 1 kinase by autophosphorylation , by the growth inhibitory proteins , RASSF 1 and NORE 1 , and by Ras , 2004 .

[77]  W. Hong,et al.  TEADs Mediate Nuclear Retention of TAZ to Promote Oncogenic Transformation* , 2009, Journal of Biological Chemistry.

[78]  Juan Huang,et al.  The apical transmembrane protein Crumbs functions as a tumor suppressor that regulates Hippo signaling by binding to Expanded , 2010, Proceedings of the National Academy of Sciences.

[79]  F. Giancotti,et al.  Shedding light on Merlin's wizardry. , 2007, Trends in cell biology.

[80]  Peter A. Lawrence,et al.  Four-Jointed Modulates Growth and Planar Polarity by Reducing the Affinity of Dachsous for Fat , 2010, Current Biology.

[81]  J. Fridlyand,et al.  Rare amplicons implicate frequent deregulation of cell fate specification pathways in oral squamous cell carcinoma , 2005, Oncogene.

[82]  Kevin J. Cheung,et al.  Tumor Suppressor LATS1 Is a Negative Regulator of Oncogene YAP* , 2008, Journal of Biological Chemistry.

[83]  S. Cohen,et al.  The Hippo Pathway Regulates the bantam microRNA to Control Cell Proliferation and Apoptosis in Drosophila , 2006, Cell.

[84]  M. DePamphilis,et al.  Regulation of gene expression at the beginning of mammalian development and the TEAD family of transcription factors. , 1998, Developmental genetics.

[85]  K. Irvine,et al.  Fat and Expanded act in parallel to regulate growth through Warts , 2007, Proceedings of the National Academy of Sciences.

[86]  C. Mein,et al.  Yes-associated protein (YAP) functions as a tumor suppressor in breast , 2008, Cell Death and Differentiation.

[87]  J Salvage,et al.  A matter of life and death. , 1981, Nursing times.

[88]  H. Ko,et al.  Glomerulocystic kidney disease in mice with a targeted inactivation of Wwtr1 , 2007, Proceedings of the National Academy of Sciences.

[89]  Fei Chen,et al.  Structural insights into the YAP and TEAD complex. , 2010, Genes & development.

[90]  Jeannie T. Lee,et al.  Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene. , 2009, Cancer cell.

[91]  Matthew Slattery,et al.  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. , 2009, Genes & development.

[92]  Janet Rossant,et al.  The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass. , 2009, Developmental cell.

[93]  N. Tapon,et al.  Combined functional genomic and proteomic approaches identify a PP2A complex as a negative regulator of Hippo signaling. , 2010, Molecular cell.

[94]  G. Halder,et al.  The bantam MicroRNA Is a Target of the Hippo Tumor-Suppressor Pathway , 2006, Current Biology.

[95]  Jianmin Zhang,et al.  Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon , 2006, Proceedings of the National Academy of Sciences.

[96]  D. Vaux,et al.  Association of mammalian sterile twenty kinases, Mst1 and Mst2, with hSalvador via C‐terminal coiled‐coil domains, leads to its stabilization and phosphorylation , 2006, The FEBS journal.

[97]  S. Lowe,et al.  Yes‐associated protein is an independent prognostic marker in hepatocellular carcinoma , 2009, Cancer.

[98]  K. Irvine,et al.  Phosphorylation-independent repression of Yorkie in Fat-Hippo signaling. , 2009, Developmental biology.

[99]  W. Hong,et al.  Structural basis of YAP recognition by TEAD4 in the hippo pathway. , 2010, Genes & development.

[100]  T. Halazonetis,et al.  Human LATS1 is a mitotic exit network kinase. , 2005, Cancer research.

[101]  I. Rodriguez,et al.  The tumor suppressor genes dachsous and fat modulate different signalling pathways by regulating dally and dally-like , 2008, Proceedings of the National Academy of Sciences.

[102]  K. Irvine,et al.  In vivo analysis of Yorkie phosphorylation sites , 2009, Oncogene.

[103]  D. Attwell,et al.  The LIM Protein Ajuba Is Recruited to Cadherin-dependent Cell Junctions through an Association with α-Catenin* , 2003, The Journal of Biological Chemistry.

[104]  Ingrid Poernbacher,et al.  The WW domain protein Kibra acts upstream of Hippo in Drosophila. , 2010, Developmental cell.

[105]  Steffen Hauptmann,et al.  Frequent hypermethylation of MST1 and MST2 in soft tissue sarcoma , 2007, Molecular carcinogenesis.

[106]  Frederic A. Fellouse,et al.  The Hippo pathway regulates Wnt/beta-catenin signaling. , 2010, Developmental cell.

[107]  M. B. Davis,et al.  breast cancer cells , 2009 .

[108]  K. Irvine,et al.  In vivo regulation of Yorkie phosphorylation and localization , 2008, Development.

[109]  K. Guan,et al.  A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP). , 2010, Genes & development.

[110]  Yaopan Mao,et al.  Drosophila lowfat, a novel modulator of Fat signaling , 2009, Development.

[111]  D. Haber,et al.  salvador Promotes Both Cell Cycle Exit and Apoptosis in Drosophila and Is Mutated in Human Cancer Cell Lines , 2002, Cell.

[112]  M. Sudol,et al.  Mst2 and Lats Kinases Regulate Apoptotic Function of Yes Kinase-associated Protein (YAP)* , 2008, Journal of Biological Chemistry.

[113]  G. Longmore,et al.  Ajuba LIM Proteins Are Negative Regulators of the Hippo Signaling Pathway , 2010, Current Biology.

[114]  D. Flagiello,et al.  SCALLOPED Interacts with YORKIE, the Nuclear Effector of the Hippo Tumor-Suppressor Pathway in Drosophila , 2008, Current Biology.

[115]  Lei Zhang,et al.  Hippo signaling regulates Yorkie nuclear localization and activity through 14-3-3 dependent and independent mechanisms. , 2010, Developmental biology.

[116]  P. Bryant,et al.  Expanded functions in the apical cell domain to regulate the growth rate of imaginal discs. , 1997, Developmental genetics.

[117]  T. Xu,et al.  Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. , 1995, Development.

[118]  S. Yang,et al.  Akt Phosphorylates MstI and Prevents Its Proteolytic Activation, Blocking FOXO3 Phosphorylation and Nuclear Translocation* , 2007, Journal of Biological Chemistry.

[119]  B. Hemmings,et al.  The MST1 and hMOB1 Tumor Suppressors Control Human Centrosome Duplication by Regulating NDR Kinase Phosphorylation , 2009, Current Biology.

[120]  M. DePamphilis,et al.  TEAD/TEF transcription factors utilize the activation domain of YAP65, a Src/Yes-associated protein localized in the cytoplasm. , 2001, Genes & development.

[121]  J. Jass,et al.  Prognostic significance of mammalian sterile20-like kinase 1 in colorectal cancer , 2007, Modern Pathology.

[122]  Xiaomu Wei,et al.  Mob as tumor suppressor is activated by Hippo kinase for growth inhibition in Drosophila , 2007, The EMBO journal.

[123]  P. Bryant,et al.  Intrinsic and Extrinsic Control of Growth in Developing Organs , 1984, The Quarterly Review of Biology.

[124]  M. Yaffe,et al.  TAZ Promotes PC2 Degradation through a SCFβ-Trcp E3 Ligase Complex , 2007, Molecular and Cellular Biology.

[125]  D. Albertson,et al.  DNA profiling of primary serous ovarian and Fallopian tube carcinomas with array comparative genomic hybridization and multiplex ligation‐dependent probe amplification , 2007, The Journal of pathology.

[126]  J. Stelling,et al.  Robustness of Cellular Functions , 2004, Cell.

[127]  R. M. Simpson,et al.  Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression , 2010, Proceedings of the National Academy of Sciences.

[128]  G. Pfeifer,et al.  RASSF1A Is Part of a Complex Similar to the Drosophila Hippo/Salvador/Lats Tumor-Suppressor Network , 2007, Current Biology.

[129]  B. Edgar,et al.  From Cell Structure to Transcription: Hippo Forges a New Path , 2006, Cell.

[130]  J. Avruch,et al.  Identification of Nore1 as a Potential Ras Effector* , 1998, The Journal of Biological Chemistry.

[131]  A. Deutman,et al.  Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12) , 1999, Nature Genetics.

[132]  M. Giovannini,et al.  Membrane organization and tumorigenesis--the NF2 tumor suppressor, Merlin. , 2005, Genes & development.

[133]  G. Halder,et al.  Boundaries of Dachsous Cadherin activity modulate the Hippo signaling pathway to induce cell proliferation , 2008, Proceedings of the National Academy of Sciences.

[134]  J. Wrana,et al.  Phosphorylation of the Tumor Suppressor Fat Is Regulated by Its Ligand Dachsous and the Kinase Discs Overgrown , 2009, Current Biology.

[135]  J. Downward,et al.  Akt phosphorylates the Yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis. , 2003, Molecular cell.

[136]  Jiandie D. Lin,et al.  TEAD mediates YAP-dependent gene induction and growth control. , 2008, Genes & development.

[137]  J. Avruch,et al.  Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras. , 2004, The Biochemical journal.

[138]  R. Fehon,et al.  Delineation of a Fat tumor suppressor pathway , 2006, Nature Genetics.

[139]  M. Wigler,et al.  Identification and Validation of Oncogenes in Liver Cancer Using an Integrative Oncogenomic Approach , 2006, Cell.

[140]  M. Yaffe,et al.  TAZ Interacts with TTF-1 and Regulates Expression of Surfactant Protein-C* , 2004, Journal of Biological Chemistry.

[141]  L. Collinson,et al.  The Hippo pathway regulates apical-domain size independently of its growth-control function , 2009, Journal of Cell Science.

[142]  W. Deng,et al.  The Hippo Pathway Promotes Notch Signaling in Regulation of Cell Differentiation, Proliferation, and Oocyte Polarity , 2008, PloS one.

[143]  Mariette Schrier,et al.  A Genetic Screen Implicates miRNA-372 and miRNA-373 As Oncogenes in Testicular Germ Cell Tumors , 2006, Cell.

[144]  Ying Li,et al.  Control of Cell Proliferation and Apoptosis by Mob as Tumor Suppressor, Mats , 2005, Cell.

[145]  Chao Qi,et al.  Identification of Fat4 as a candidate tumor suppressor gene in breast cancers , 2009, International journal of cancer.

[146]  K. Mimori,et al.  Clinical significance of the loss of MATS1 mRNA expression in colorectal cancer. , 2007, International journal of oncology.

[147]  Ryan S. Udan,et al.  Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway , 2003, Nature Cell Biology.

[148]  Daniel Birnbaum,et al.  Integrated profiling of basal and luminal breast cancers. , 2007, Cancer research.

[149]  Robert Tibshirani,et al.  Array-based comparative genomic hybridization identifies localized DNA amplifications and homozygous deletions in pancreatic cancer. , 2005, Neoplasia.

[150]  M. Giovannini,et al.  The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. , 2010, Developmental cell.

[151]  B. Wang,et al.  The Drosophila Ste20 family kinase dMST functions as a tumor suppressor by restricting cell proliferation and promoting apoptosis. , 2003, Genes & development.

[152]  G. Feldmann,et al.  Elucidation of a Universal Size-Control Mechanism in Drosophila and Mammals , 2007, Cell.

[153]  Ju-Seog Lee,et al.  Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver , 2010, Proceedings of the National Academy of Sciences.

[154]  H. Aburatani,et al.  Multiple renal cysts, urinary concentration defects, and pulmonary emphysematous changes in mice lacking TAZ. , 2008, American journal of physiology. Renal physiology.

[155]  E. Krebs,et al.  Both Phosphorylation and Caspase-mediated Cleavage Contribute to Regulation of the Ste20-like Protein Kinase Mst1 during CD95/Fas-induced Apoptosis* , 2001, The Journal of Biological Chemistry.

[156]  G. Karsenty,et al.  Transcriptional Coactivation of Bone-Specific Transcription Factor Cbfa1 by TAZ , 2003, Molecular and Cellular Biology.

[157]  H. Kiyonari,et al.  Redundant Roles of Tead1 and Tead2 in Notochord Development and the Regulation of Cell Proliferation and Survival , 2008, Molecular and Cellular Biology.

[158]  D. Tomchick,et al.  Structural and functional analysis of the YAP-binding domain of human TEAD2 , 2010, Proceedings of the National Academy of Sciences.

[159]  N. Perrimon,et al.  Drosophila Stardust interacts with Crumbs to control polarity of epithelia but not neuroblasts , 2001, Nature.

[160]  G. Rodan,et al.  Mapping of MST1 Kinase Sites of Phosphorylation , 2002, The Journal of Biological Chemistry.

[161]  Wei Zhou,et al.  Promoter hypermethylation-mediated down-regulation of LATS1 and LATS2 in human astrocytoma , 2006, Neuroscience Research.

[162]  Yaopan Mao,et al.  Dachs: an unconventional myosin that functions downstream of Fat to regulate growth, affinity and gene expression in Drosophila , 2006, Development.

[163]  G. Pfeifer,et al.  The RASSF proteins in cancer; from epigenetic silencing to functional characterization. , 2009, Biochimica et biophysica acta.

[164]  A. Le Bivic,et al.  Crumbs proteins in epithelial morphogenesis. , 2009, Frontiers in bioscience.

[165]  P Robin Hiesinger,et al.  Shar-pei mediates cell proliferation arrest during imaginal disc growth in Drosophila , 2002, Development.

[166]  K. Harvey,et al.  Differential requirement of Salvador-Warts-Hippo pathway members for organ size control in Drosophila melanogaster , 2010, Development.

[167]  S. Pulst,et al.  Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2 , 1993, Nature.

[168]  H. Sasaki,et al.  Mammalian Tead proteins regulate cell proliferation and contact inhibition as transcriptional mediators of Hippo signaling , 2008, Development.

[169]  Y. Kong,et al.  A crucial role of WW45 in developing epithelial tissues in the mouse , 2008, The EMBO journal.

[170]  W. Tiana,et al.  Structural and functional analysis of the YAP-binding domain of human TEAD 2 , 2010 .

[171]  Xiaomu Wei,et al.  Mob as tumor suppressor is activated at the cell membrane to control tissue growth and organ size in Drosophila. , 2010, Developmental biology.

[172]  Sho Fujisawa,et al.  Nuclear CDKs Drive Smad Transcriptional Activation and Turnover in BMP and TGF-β Pathways , 2009, Cell.

[173]  Esteban O. Mazzoni,et al.  The Growth Regulators warts/lats and melted Interact in a Bistable Loop to Specify Opposite Fates in Drosophila R8 Photoreceptors , 2005, Cell.

[174]  Brian A. Hemmings,et al.  NDR Kinase Is Activated by RASSF1A/MST1 in Response to Fas Receptor Stimulation and Promotes Apoptosis , 2008, Current Biology.

[175]  K. Katagiri,et al.  RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1 , 2003, Nature Immunology.

[176]  E. White,et al.  Role of the polarity determinant crumbs in suppressing mammalian epithelial tumor progression. , 2008, Cancer research.

[177]  R. Jaenisch,et al.  YAP1 Increases Organ Size and Expands Undifferentiated Progenitor Cells , 2007, Current Biology.

[178]  Zhengyu Zha,et al.  TAZ Promotes Cell Proliferation and Epithelial-Mesenchymal Transition and Is Inhibited by the Hippo Pathway , 2008, Molecular and Cellular Biology.

[179]  P J Bryant,et al.  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. , 1995, Genes & development.

[180]  C. Haipek,et al.  The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44. , 2001, Genes & development.

[181]  G. Halder,et al.  The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis , 2006, Nature Cell Biology.

[182]  D. Calvisi,et al.  The Hippo–Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis , 2010, Proceedings of the National Academy of Sciences.

[183]  J. Avruch,et al.  Mst 1 and Mst 2 Maintain Hepatocyte Quiescence and Suppress Hepatocellular Carcinoma Development through Inactivation of the Yap 1 Oncogene , 2011 .

[184]  Dragana Rogulja,et al.  Morphogen control of wing growth through the Fat signaling pathway. , 2008, Developmental cell.

[185]  K. Reid,et al.  Yap is a novel regulator of C2C12 myogenesis. , 2010, Biochemical and biophysical research communications.

[186]  D. Tyler,et al.  Expanded and fat regulate growth and differentiation in the Drosophila eye through multiple signaling pathways. , 2007, Developmental biology.