Mammalian Hippo pathway: From development to cancer and beyond

Journal of Biochemistry

Volumn 149, Issue 4, 2011, Pages 361-379

  Bao, Yijun ^a,b   Hata, Yutaka ^a,c   Ikeda, Mitsunobu ^a   Withanage, Kanchanamala ^a  

^a TOKYO MEDICAL AND DENTAL UNIVERSITY   (Japan)

^b CHINA MEDICAL UNIVERSITY   (China)

^c NONE   (Japan)

Author keywords

apoptosis; cancer; kinase; regeneration; signal transduction

Indexed keywords

FAT; MAMMALIAN STE20 LIKE KINASE 1; MAMMALIAN STE20 LIKE KINASE 2; MERLIN; NUCLEAR DBF2 RELATED KINASE 1; PHOSPHOTRANSFERASE; PROTEIN; RAS ASSOCIATION DOMAIN FAMILY PROTEIN 1A; SAV; TRANSCRIPTIONAL COACTIVATOR WITH PDZ BINDING MOTIF; UNCLASSIFIED DRUG; YES ASSOCIATED PROTEIN;

APOPTOSIS; CANCER INHIBITION; CARCINOGENESIS; CELL DIFFERENTIATION; CELLULAR DISTRIBUTION; CHEMICAL STRUCTURE; DROSOPHILA; GENE ACTIVATION; GENE IDENTIFICATION; GENE INTERACTION; GENE LOCATION; GENE MUTATION; GENE OVEREXPRESSION; GENE SILENCING; GENETIC ANALYSIS; GENETIC TRANSCRIPTION; HEMATOPOIETIC CELL; HIPPO PATHWAY; HOMEOSTASIS; HUMAN; MAMMAL; MOLECULAR INTERACTION; NEOPLASM; NONHUMAN; ORGAN SIZE; PDZ DOMAIN; PROTEIN INTERACTION; PROTEIN PROCESSING; REVIEW; SIGNAL TRANSDUCTION; STEM CELL; TISSUE; TISSUE GROWTH; TISSUE REGENERATION; TUMOR SUPPRESSOR GENE;

DROSOPHILA MELANOGASTER; MAMMALIA;

EID: 79953207329     PISSN: 0021924X     EISSN: 17562651     Source Type: Journal    
DOI: 10.1093/jb/mvr021     Document Type: Review

References (255)

1. Pan, D. (2010) The Hippo signaling pathway in devel-opment and cancer. Dev. Cell 19, 491-505
2. Zhao, B., Li, L., and Guan, K.L. (2010) Hippo signaling at a glance. J. Cell Sci. 123, 4001-4006
3. Zhao, B., Li, L., Lei, Q., and Guan, K.L. (2010) The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version. Genes Dev. 24, 862-874
4. Grusche, F.A., Richadson, H.E., and Harvey, K.F. (2010) Upstream regulation of the hippo size control pathway. Curr. Biol. 20, R574-R582
5. Sudol, M. and Harvey, K.F. (2010) Modularity in the Hippo signaling pathway. Trends Biochem. Sci. 35, 627-633
6. Chan, S.W., Lim, C.J., Chen, L., Chong, Y.F., Huang, C., Song, H., and Hong, W. (2010) The hippo pathway in biological control and cancer development. J. Cell. Physiol. 226, 928-939
7. Parsons, L.M., Grzeschik, N.A., Allott, M.L., and Richardson, H.E. (2010) Lgl/aPKC and Crb regulate the Salvador/warts/hippo pathway. Fly 4, 288-293
8. Mahoney, P.A., Weber, U., Onofrechuk, P., Biessmann, H., Bryant, P.J., and Goodman, C.S. (1991) The fat tumor suppressor gene in Drosophila encodes a novel member of the cadherin gene superfamily. Cell 67, 853-868 (Pubitemid 121001500)
9. Boedigheimer, M. and Laughon, A. (1993) Expanded: A gene involved in the control of cell proliferation in imaginal discs. Development 118, 1291-1301 (Pubitemid 23252416)
10. Xu, T., Wang, W., Zhang, S., Stewart, R.A., and Yu, W. (1995) Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. Development 121, 1053-1063
11. Justice, R.W., Zilian, O., Woods, D.F., Noll, M., and Bryant, P.J. (1995) The Drosophila tumor suppressor gene warts encodes a homolog of human myotonic dys-trophy kinase and is required for the control of cell shape and proliferation. Genes Dev. 9, 534-546
12. McCartney, B.M. and Fehon, R.G. (1996) Distinct cellular and subcellular patterns of expression imply distinct functions for the Drosophila homologues of moesin and the neurofibromatosis 2 tumor suppressor, merlin. J. Cell Biol. 133, 843-852 (Pubitemid 26163343)
13. Tapon, N., Harvey, K.F., Bell, D.W., Wahrer, D.C., Schiripo, T.A., Haber, D.A., and Hariharan, I.K. (2002) salvador promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines. Cell 110, 467-478 (Pubitemid 35232290)
14. Kango-Singh, M., Nolo, R., Tao, C., Verstreken, P., Hiesinger, P.R., Bellen, H.J., and Halder, G (2002) Shar-pei mediates cell proliferation arrest during imagi-nal disc growth in Drosophila. Development 129, 5719-5730 (Pubitemid 36054615)
15. Harvey, K.F., Pfleger, C.M., and Hariharan, I.K. (2003) The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis. Cell 114, 457-467 (Pubitemid 37100994)
16. Wu, S., Huang, J., Dong, J, and Pan, D. (2003) hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts. Cell 114, 445-456 (Pubitemid 37100993)
17. Jia, J., Zhang, W., Wang, B., Trinko, R., and Jiang, J. (2003) The Drosophila Ste20 family kinase dMST functions as a tumor suppressor by restricting cell pro-liferation and promoting apoptosis. Genes Dev. 17, 2514-2519 (Pubitemid 37271421)
18. Udan, R.S., Kango-Singh, M., Nolo, R., Tao, C., and Halder, G (2003) Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway. Nat. Cell Biol. 5, 914-920 (Pubitemid 37220698)
19. Pantalacci, S., Tapon, N., and Leopold, P. (2003) The Salvador partner Hippo promotes apoptosis and cell-cycle exit in Drosophila. Nat. Cell Biol. 5, 921-927 (Pubitemid 37220699)
20. Lai, Z.C., Wei, X., Shimizu, T., Ramos, E., Rohrbaugh, M., Nikolaidis, N., Ho, L.L., and Li, Y. (2005) Control of cell proliferation and apoptosis by mob as tumor suppressor, mats. Cell 120, 675-685 (Pubitemid 40343079)
21. Huang, J., Wu, S., Barrera, J., Matthews, K., and Pan, D. (2005) The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila homolog of YAP. Cell 122, 421-434 (Pubitemid 41127143)
22. Dong, J., Feldmann, G., Huang, J., Wu, S., Zhang, N., Comerford, S.A., Gayyed, M.F., Anders, R.A., Maitra, A., and Pan, D. (2007) Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell 130, 1120-1133 (Pubitemid 47410268)
23. Wu, S., Liu, Y., Zheng, Y., Dong, J., and Pan, D. (2008) The TEAD/TEF family protein Scalloped mediates transcriptional output of the Hippo growth-regulatory pathway. Dev. Cell 14, 388-398
24. Goulev, Y., Fauny, J.D., Gonzalez-Marti, B., Flagiello, D., Silber, J., and Zider, A. (2008) SCALLOPED inter-acts with YORKIE, the nuclear effector of the hippo tumor-suppressor pathway in Drosophila. Curr. Biol. 18, 435-441
25. Clark, H.F., Brentrup, D., Schneitz, K., Bieber, A., Goodman, C., and Noll, M. (1995) Dachsous encodes a member of the cadherin superfamily that controls im-aginal disc morphogenesis in Drosophila. Genes Dev. 9, 1530-1542
26. Strutt, H. and Strutt, D. (2002) Nonautonomous pla-nar polarity patterning in Drosophila: dishevelled-independent functions offrizzled. Dev. Cell3, 851-863 (Pubitemid 35460785)
27. Ma, D., Yang, C.H., McNeill, H., Simon, M.A., and Axelrod, J.D. (2003) Fidelity in planar cell polarity signaling. Nature 421, 543-547 (Pubitemid 36168448)
28. Matakatsu, H. and Blair, S.S. (2004) Interactions be-tween Fat and Dachsous and the regulation of planar cell polarity in the Drosophila wing. Development 131, 3785-3794 (Pubitemid 39199385)
29. Silva, E., Tsatskis, Y., Gardano, L., Tapon, N., and McNeill, H. (2006) The tumor suppressor gene fat con-trols tissue growth upstream of expanded in the hippo signaling pathway. Curr. Biol. 16, 2081-2089 (Pubitemid 44692094)
30. Willecke, M., Hamaratoglu, F., Kango-Singh, M., Udan, R., Chen, C.L., Tao, C., Zhang, X., and Halder, G (2006) The fat cadherin acts through the hippo tumor-suppressor pathway to regulate tissue size. Curr. Biol. 16, 2090-2100 (Pubitemid 44692095)
31. Benett, F.C. and Harvey, K.F. (2006) Fat cadherin modulates organ size in Drosophila via the Salvador/Warts/Hippo signaling pathway. Curr. Biol. 16, 2101-2110 (Pubitemid 44692100)
32. Ishikawa, H.O., Takeuchi, H., Haltiwanger, R.S., and Irvine, K.D. (2008) Four-jointed is a Golgi kinase that phosphorylates a subset of cadherin domains. Science 321, 401-404 (Pubitemid 352029975)
33. Willecke, M., Hamaratoglu, F., Sansores-Garcia, L., Tao, C., and Halder, G (2008) Boundaries of Dachsous Cadherin activity modulate the Hippo signaling pathway to induce cell proliferation. Proc. Natl. Acad. Sci. USA 105, 14897-14902
34. Brittle, A.L., Repiso, A., Casal, J., Lawrence, P.A., and Strutt, D. (2010) Four-jointed modulates growth and planar polarity by reducing the affinity of dachsous for Fat. Curr. Biol. 20, 803-810
35. Simon, M.A., Xu, A., Ishikawa, H.O., and Irvine, K.D. (2010) Modulation of fat:dachsous binding by the cad-herin domain kinase four-jointed. Curr. Biol. 20, 811-817
36. Cho, E., Feng, Y., Rauskolb, C., Maitra, S., Fehon, R., and Irvine, K.D. (2006) Delineation of a Fat tumor suppressor pathway. Nat. Genet. 38, 1142-1150 (Pubitemid 44470359)
37. Mao, Y., Rauskolb, C., Cho, E., Hu, W.L., Hayter, H., Minihan, G., Katz, F.N., and Irvine, K.D. (2006) Dachs: an unconventional myosin that functions downstream of Fat to regulate growth, affinity and gene expression in Drosophila. Development 133, 2539-2551 (Pubitemid 44123403)
38. Matakatsu, H. and Blair, S.S. (2008) The DHHC palmitoyltransferase approximated regulates Fat signal-ing and Dachs localization and activity. Curr. Biol. 18, 1390-1395
39. Sopko, R., Silva, E., Clayton, L., Gardano, L., Barrios-Rodiles, M., Wrana, J., Varelas, X., Arbouzova, N.I., Shaw, S., Saburi, S., Matakatsu, H., Blair, S., and McNeill, H. (2009) Phosphorylation of the tumor sup-pressor fat is regulated by its ligand Dachsous and the kinase discs overgrown. Curr. Biol. 19, 1112-1117
40. Feng, Y. and Irvine, K.D. (2009) Processing and phos-phorylation of the Fat receptor. Proc. Natl. Acad. Sci. USA 106, 11989-11994
41. Mao, Y., Kucuk, B., and Irvine, K.D. (2009) Drosophila lowfat, a novel modulator of Fat signaling. Development 136, 3223-3233
42. Fanto, M., Clayton, L., Meredith, J., Hardiman, K., Charroux, B., Kerridge, S., and McNeill, H. (2003) The tumor-suppressor and cell adhesion molecule Fat controls planar polarity via physical interactions with Atrophin, a transcriptional co-repressor. Development 130, 763-774 (Pubitemid 36240584)
43. Assemat, E., Bazellieres, E., Pallesi-Pocachard, E., Le Bivic, A., and Massey-Harroche, D. (2008) Polarity complex proteins. Biochim. Biophys. Acta 1778, 614-630 (Pubitemid 351317801)
44. Ling, C., Zheng, Y., Yin, F., Yu, J., Huang, J., Hong, Y., Wu, S., and Pan, D. (2010) The apical transmem-brane protein Crumbs functions as a tumor suppressor that regulates Hippo signaling by binding to Expanded. Proc. Natl. Acad. Sci. USA 107, 10532-10537
45. Robinson, B.S., Huang, J., Hong, Y., and Moberg, K.H. (2010) Crumbs regulates Salvador/Warts/Hippo signaling in Drosophila via the FERM-domain protein Expanded. Curr. Biol. 20, 582-590
46. Chen, C.L., Gajewski, K.M., Hamaratoglu, F., Bossuyt, W., Sansores-Garcia, L., Tao, C., and Halder, G. (2010) The apical-basal cell polarity determinant Crumbs regulates Hippo signaling in Drosophila. Proc. Natl. Acad. Sci. USA 107, 15810-15815
47. Hamaratoglu, F., Willecke, M., Kango-Singh, M., Nolo, R., Hyun, E., Tao, C., Jafar-Nejad, H., and Halder, G (2006) The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signaling to regulate cell proliferation and apoptosis. Nat. Cell Biol. 8, 27-36 (Pubitemid 43064794)
48. Feng, Y. and Irvine, K.D. (2007) Fat and expanded act in parallel to regulate growth through warts. Proc. Natl. Acad. Sci. USA 104, 20362-20367
49. Yu, J., Zheng, Y., Dong, J., Klusza, S., Deng, W.M., and Pan, D. (2010) Kibra functions as a tumor sup-pressor protein that regulates Hippo signaling in con-junction with Merlin and Expanded. Dev. Cell 18, 288-299
50. Genevet, A., Wehr, M.C., Brain, R., Thompson, B.J., and Tapon, N. (2010) Kibra is a regulator of the Salvador/Warts/Hippo signaling network. Dev. Cell 18, 300-308
51. Baumgartner, R., Poermbacher, I., Buser, N., Hafen, E., and Stocker, H. (2010) The WW domain protein Kibra acts upstream of Hippo in Drosophila. Dev. Cell 18, 309-316
52. Polesello, C., Huelsmann, S., Brown, N.H., and Tapon, N. (2006) The Drosophila RASSF homolog antagonizes the hippo pathway. Curr. Biol. 16, 2459-2465 (Pubitemid 44894911)
53. Ribeiro, P.S., Josue, F., Wepf, A., Wehr, M.C., Rinner, O., Kelly, G., Tapon, N., and Gstaiger, M. (2010) Combined functional genomic and proteomic approaches identify a PP2A complex as a negative regulator of Hippo signaling. Mol. Cell 39, 521-534
54. Das Thakur, M., Feng, Y., Jagannathan, R., Seppa, M.J., Skeath, J.B., and Longmore, G.D. (2010) Ajuba LIM proteins are negative regulators of the Hippo sig-naling pathway. Curr. Biol. 20, 657-662
55. Grzeschik, N.A., Parsons, L.M., Allott, M.L., Harvey, K.F., and Richardson, H.E. (2010) Lgl, aPKC, and Crumbs regulate the Salvador/Warts/Hippo pathway through two distinct mechanisms. Curr. Biol. 20, 573-581
56. Hamaratoglu, F., Gajewski, K., Sansores-Garcia, L., Morrison, C., Tao, C., and Halder, G (2009) The Hippo tumor-suppressor pathway regulates apical-domain size in parallel to tissue growth. J. Cell Sci. 122, 2351-2359
57. Genevet, A., Polesello, C., Blight, K., Robertson, F., Collinson, L.M., Pichaud, F., and Tapon, N. (2009) The Hippo pathway regulates apical-domain size inde-pendently of its growth-control function. J. Cell Sci. 122, 2360-2370
58. Colombani, J., Polesello, C., Josue, F., and Tapon, N. (2006) Dmp53 activates the Hippo pathway to promote cell death in response to DNA damage. Curr. Biol. 16, 1453-1458 (Pubitemid 44066776)
59. Rouleau, G.A., Merel, P., Lutchman, M., Sanson, M., Zucman, J., Marineau, C., Hoang-Xuan, K., Demczuk, S., Desmaze, C., Plougastel, B., Plust, S.M., Lenoir, G., Bijlsma, E., Fashold, R., Dumaski, J., de Jong, P., Parry, D., Eldrige, R., Aurias, A., Delattre, O., and Thomas, G (1993) Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature 363, 515-521 (Pubitemid 23186636)
60. Trofatter, J.A., MacCollin, M.M., Rutter, J.L., Murrell, J.R., Duyao, M.P., Parry, D.M., Eldridge, R., Kley, N., Menon, A.G., Pulaski, K., Haase, V.H., Ambrose, C.M., Munroe, D., Bove, C., Haines, J.L., Martuza, R.L., MacDonald, M.E., Seizinger, B.R., Short, M.P., Buckler, A.J., and Gusella, J.F. (1993) A novel moesin-, ezrin-, radixin-like gene is a candidate for the neuro-fibromatosis 2 tumor suppressor. Cell 72, 791-800 (Pubitemid 23093886)
61. Sherman, L., Xu, H.M., Geist, R.T., Saporito-Irwin, S., Howells, N., Ponta, H., Herrlich, P., and Gutmann, D.H. (1997) Interdomain binding mediates tumor growth suppression by the NF2 gene product. Oncogene 15, 2505-2509 (Pubitemid 27503537)
62. Shaw, R.J., McClatchey, A.I., and Jacks, T. (1998) Regulation of the neurofibromatosis type 2 tumor suppressor protein, merlin, by adhesion and growth arrest stimuli. J. Biol. Chem. 273, 7757-7764 (Pubitemid 28152808)
63. Shaw, R.J., Paez, J.G., Curto, M., Yaktine, A., Pruitt, W.M., Saotome, I., O'Bryan, J.P., Gupta, V., Ratner, N., Der, C.J., Jacks, T., and McClatchey, A.I. (2001) The Nf2 tumor suppressor, merlin, functions in Rac-dependent signaling. Dev. Cell 1, 63-72 (Pubitemid 33586069)
64. Creasy, C.L. and Chernoff, J. (1995) Cloning and char-acterization of a member of the MST subfamily of Ste20-like kinases. Gene 167, 303-306 (Pubitemid 26035917)
65. Taylor, L.K., Wang, H.C., and Erikson, R.L. (1996) Newly identified stress-responsive protein kinases, Krs-1 and Krs-2. Proc. Natl. Acad. Sci. USA 93, 10099-10104 (Pubitemid 26314581)
66. Tao, W., Zhang, S., Turenchalk, G.S., Stewart, R.A., St John, M.A., Chen, W., and Xu, T. (1999) Human homologue of the Drosophila melanogaster lats tumor suppressor modulates CDC2 activity. Nat. Genet. 21, 177-181 (Pubitemid 29070362)
67. Yabuta, N., Fujii, T., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Nishiguchi, H., Endo, Y., Toji, S., Tanaka, H., Nishimune, Y., and Nojima, H. (2000) Structure, expression, and chromosome mapping of LATS2, a mammalian homologue of the Drosophila tumor suppressor gene lats/warts. Genomics 63, 263-270 (Pubitemid 30131950)
68. Hori, T., Takaori-Konda, A., Kamikubo, Y., and Uchiyama, T. (2000) Molecular cloning of a novel human protein kinase, kpm, that is homologous to warts/lats, a Drosophila tumor suppressor. Oncogene 22, 3101-3109 (Pubitemid 30438467)
69. Luca, F.C. and Winey, M. (1998) MOB1, an essential yeast gene required for completion of mitosis and main-tenance of ploidy. Mol. Biol. Cell 9, 29-46 (Pubitemid 28065279)
70. Moreno, C.S., Lane, W.S., and Pallas, D.C. (2001) A mammalian homolog of yeast MOB1 is both a member and a putative substrate of striatin family-protein phos-phatase 2A complexes. J. Biol. Chem. 276, 24253-24260
71. Sudol, M. (1994) Yes-associated protein (YAP65) is a proline-rich phosphoprotein that binds to the SH3 domain of the Yes proto-oncogene product. Oncogene 9, 2145-2152 (Pubitemid 24228662)
72. Bertini, E., Oka, T., Sudol, M., Strano, S., and Blandino, G (2009) YAP: at the crossroad between transformation and tumor suppression. Cell Cycle 8, 49-57
73. Kanai, F., Marignani, P.A., Sarbassova, D., Yagi, R., Hall, R.A., Donowitz, M., Hisaminato, A., Fujiwara, T., Ito, Y., Cantley, L.C., and Yaffe, M.B. (2000) TAZ: a novel transcriptional coactivator regulated by inter-actions with 14-3-3 and PDZ domain proteins. EMBO J. 19, 6778-6791 (Pubitemid 32011671)
74. Gunn-Moore, F.J., Welsh, G.I., Herron, L.R., Brannigan, F., Venkateswarlu, K., Gillespie, S., Bradwein-Gensler, M., Madan, R., Tavare, J.M., Brophy, P.J., Prystowsky, M.B., and Guild, S. (2005) A novel 4.1 ezrin radixin moesin (FERM)-containing protein 'Willin'. FEBS Lett. 579, 5089-5094 (Pubitemid 41242858)
75. Kilili, G.K. and Kyriakis, J.M. (2010) Mammalian Ste20-like kinase (Mst2) indirectly supports Raf-1/ERK pathway activity via maintenance of protein phosphatase-2A catalytic subunit levels and consequent suppression of inhibitory Raf-1 phosphorylation. J. Biol. Chem. 285, 15076-15087
76. Ishiuchi, T., Misaki, K., Yonemura, S., Takeichi, M., and Tanoue, T. (2009) Mammalian Fat and Dachsous cadherins regulate apical membrane organization in the embryonic cerebral cortex. J. Cell Biol. 185, 959-967
77. Qi, C., Zhu, Y.T., Hu, L., and Zhu, Y.J. (2009) Identification of Fat4 as a candidate tumor suppressor gene in breast cancers. Int. J. Cancer 124, 793-798
78. Sainio, M., Zhao, F., Heiska, L., Turunen, O., den Bakker, M., Zwarthoff, E., Lutchman, M., Rouleau, G.A., Jaaskelainen, J., Vaheri, A., and Carpen, O. (1997) Neurofibroamatosis 2 tumor sup-pressor protein colocalizes with ezrin and CD44 and associates with actin-containing cytoskeleton. J. Cell Biol. 110, 2249-2260 (Pubitemid 27448369)
79. Morrison, H., Sherman, L.S., Legg, J., Banine, F., Isacke, C., Haipek, C.A., Gutmann, D.H., Ponta, H., and Herrlich, P. (2001) The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44. Genes Dev. 15, 968-980 (Pubitemid 32323547)
80. Xu, Y., Stamenkovic, I., and Yu, Q. (2010) CD44 at-tenuates activation of the hippo signaling pathway and is a prime therapeutic target for glioblastoma. Cancer Res. 70, 2455-2464
81. + exchange, is a common interactor for merlin and ERM (MERM) proteins. J. Biol. Chem. 273, 1273-1276 (Pubitemid 28133639)
82. Volz, J.W., Weinman, E.J., and Shenolikar, S. (2001) Expanding the role of NHERF, a PDZ-domain con-taining protein adapter, to growth regulation. Oncogene 20, 6309-6314 (Pubitemid 32977839)
83. Yi, C. and Kissil, J.L. (2010) Merlin in organ size control and tumorigenesis: Hippo versus EGFR? Genes Dev. 24, 1673-1679
84. c-Yes to the apical compartment of airway epithelia by association with EBP50. J. Cell Biol. 147, 879-890
85. Radu, M. and Chernoff, J. (2009) The DeMSTification of mammalian Ste20 kinases. Curr. Biol. 19, R421-425
86. Ling, P., Lu, T.J., Yuan, C.J., and Lai, M.D. (2007) Biosignaling of mammalian Ste20-related kinases. Cell Signal. 20, 1237-1247
87. Yang, X., Yu, K., Hao, Y., Li, D.M., Stewart, R., Insogna, K.L., and Xu, T. (2004) LATS1 tumor suppressor affects cytokinesis by inhibiting LIMK1. Nat. CellBiol. 6, 609-617 (Pubitemid 38960918)
88. Kuninaka, S., Nomura, M., Hirota, T., Iida, S., Hara, T., Honda, S., Kunitoku, N., Sasayama, T., Arima, Y., Marumoto, T., Koja, K., Yonehara, S., and Saya, H. (2005) The tumor suppressor WARTS activates the Omi/HtrA2-dependent pathway of cell death. Oncogene 24, 5287-5298 (Pubitemid 43080099)
89. Kuninaka, S., Iida, S.I., Hara, T., Nomura, M., Naoe, H., Morisaki, T., Nitta, M., Arima, Y., Mimori, T., Yonehara, S., and Saya, H. (2007) Serine protease Omi/HtrA2 targets WARTS kinase to control cell pro-liferation. Oncogene 26, 2395-2406 (Pubitemid 46597271)
90. Okada, T., You, L., and Giancotti, F.G. (2007) Shedding light on Merlin's wizardry. Trends Cell Biol. 17, 222-229 (Pubitemid 46679247)
91. McClatchey, A.I. and Fehon, R.G. (2009) Merlin and the ERM proteins-regulators of receptor distribution and signaling at the cell cortex. Trends Cell Biol. 19, 198-206
92. Stamenkovic, I. and Yu, Q. (2010) Merlin, a "magic" linker between extracellular cues and intracellular signaling pathways that regulate cell motility, prolifer-ation, and survival. Curr. Protein Pept. Sci. 11, 471-484
93. Xiao, G.H., Beeser, A., Chernoff, J., and Testa, J.R. (2002) p21-activated kinase links Rac/Cdc42 signaling to merlin. J. Biol. Chem. 277, 883-886 (Pubitemid 34968830)
94. Kissil, J.L., Johnson, K.C., Eckman, M.S., and Jacks, T. (2002) Merlin phosphorylation by p21-activated kinase 2 and effects of phosphorylation on merlin localization. J. Biol. Chem. 277, 10394-10399 (Pubitemid 34968159)
95. Jin, H., Sperka, T., Herrlich, P., and Morrison, H. (2006) Tumorigenic transformation by CPI-17 through inhibition of a merlin phosphatase. Nature 442, 576-579 (Pubitemid 44167917)
96. Curto, M., Cole, B.K., Lallemand, D., Liu, C.H., and McClatchey, A.I. (2007) Contact-dependent inhibition of EGFR signaling by Nf2/Merlin. J. Cell Biol. 177, 893-903 (Pubitemid 46873094)
97. Maitra, S., Kulikauskas, R.M., Gavilan, H., and Fehon, R.G. (2006) The tumor suppressors Merlin and Expanded function cooperatively to modulate receptor endocytosis and signaling. Curr. Biol. 16, 702-709
98. Zhang, N., Bai, H., David, K.K., Dong, J., Zheng, Y., Cai, J., Giovannini, M., Liu, P., Anders, R.A., and Pan, D. (2010) The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeo-stasis in mammals. Dev. Cell 19, 27-38
99. Benhamouche, S., Curto, M., Saotome, I., Gladden, A.B., Liu, C.H., Giovannini, M., and McClatchey, A.I. (2010) Nf2/Merlin controls progenitor homeostasis and tumorigenesis in the liver. Genes Dev. 24, 1718-1730
100. DC F1 in the nucleus. Cell 140, 477-490
101. Graves, J.D., Gotoh, Y., Draves, K.E., Ambrose, D., Han, D.K., Wright, M., Chernoff, J., Clark, E.A., and Krebs, E.G. (1998) Caspase-mediated activation and in-duction of apoptosis by the mammalian Ste20-like kinase Mst1. EMBO J. 17, 2224-2234 (Pubitemid 28171908)
102. Lee, K.K., Murakawa, M., Nishida, E., Tsubuki, S., Kawashima, S., Sakamaki, K., and Yonehara, S. (1998) Proteolytic activation of MST/Krs, STE20-related protein kinase, by caspase during apoptosis. Oncogene 16, 3029-3037 (Pubitemid 28297725)
103. Ura, S., Masuyama, N., Graves, J.D., and Gotoh, Y. (2001) Caspase cleavage of MST1 promotes nuclear translocation and chromatin condensation. Proc. Natl. Acad. Sci. USA 98, 10148-10153 (Pubitemid 32802989)
104. Jang, S.W., Yang, S.J, Srinivasan, S., and Ye, K. (2007) Akt phosphorylates MstI and prevents its proteolytic activation, blocking FOXO3 phosphorylation and nu-clear translocation. J. Biol. Chem. 282, 30836-30844 (Pubitemid 350035233)
105. Yuan, Z., Kim, D., Shu, S., Wu, J., Guo, J., Xiao, L., Kaneko, S., Coppola, D., and Cheng, J.Q. (2010) Phosphoinositide 3-kinase/Akt inhibits MST1-mediated pro-apoptotic signaling through phosphorylation of threonine 120. J. Biol. Chem. 285, 3815-3824
106. Romano, D., Matallanas, D., Weitsman, G., Preisinger, C., Ng, T., and Kolch, W. (2010) Proapoptotic kinase MST2 coordinates signaling crosstalk between RASSF1A, Raf-1, and Akt. Cancer Res. 70, 1195-1203
107. Kim, D., Shu, S., Coppola, M.D., Kaneko, S., Yuan, Z.Q., and Cheng, J.Q. (2010) Regulation ofproapopto-tic mammalian ste20-like kinase MST2 by the IGF1-Akt pathway. PLoS ONE 5, e9616
108. Qiao, M., Wang, Y., Xu, X., Lu, J., Dong, Y., Tao, W., Stein, J., Stein, G.S., Iglehart, J.D., Shi, Q., and Pardee, A.B. (2010) Mst1 is an interacting protein that mediates PHLPPs' induced apoptosis. Mol. Cell 38, 512-523
109. Ura, S., Nishina, H., Gotoh, Y., and Katada, T. (2007) Activation of the c-Jun N-terminal kinase pathway by MST1 is essential and sufficient for the induction of chromatin condensation during apoptosis. Mol. Cell. Biol. 27, 5514-5522 (Pubitemid 47124403)
110. Cheung, W.L., Ajiro, K., Samejima, K., Kloc, M., Cheung, P., Mizzen, C.A., Beeser, A., Etkin, L.D., Chernoff, J., Earnshaw, W.C., and Allis, C.D. (2003) Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase. Cell 113, 507-517 (Pubitemid 36603322)
111. Wen, W., Zhu, F., Zhang, J., Keum, Y.S., Zykova, T., Yao, K., Peng, C., Zheng, D., Cho, Y.Y., Ma, W.Y., Bode, A.M., and Dong, Z. (2010) MST1 promotes apoptosis through phosphorylation of histone H2AX. J. Biol. Chem. 285, 39108-39116
112. Choi, J., Oh, S., Lee, D., Oh, H.J., Park, J.Y., Lee, S.B., and Lim, D.S. (2009) Mst1-FoxO signaling protects naive T lymphocytes from cellular oxidative stress in mice. PLoS ONE 4, e8011
113. Lehtinen, M.K., Yuan, Z., Boag, P.R., Yang, Y., Villen, J., Becker, E.B., DiBacco, S., de la Iglesia, N., Gygi, S., Blackwell, T.K., and Bonni, A. (2006) A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell 125, 987-1001 (Pubitemid 43795191)
114. Yuan, Z., Lehtinen, M.K., Merlo, P., Villen, J., Gygi, S., and Bonni, A. (2009) Regulation of neuronal cell death by MST1-FOXO1 signaling. J. Biol. Chem. 284, 11285-11292
115. Mardin, B.R., Lange, C., Baxter, J.E., Hardy, T., Scholz, S.R., Fry, A.M., and Schiebel, E. (2010) Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction. Nat. CellBiol. 12, 1166-1176
116. Oh, H.J., Kim, M.J., Song, S.J., Kim, T., Lee, D., Kwon, S.H., Choi, E.J., and Lim, D.S. (2010) MST1 limits the kinase activity of aurora B to promote stable kinetochore-microtubule attachment. Curr. Biol. 20, 416-422
117. Lin, Y., Khokhlatchev, A., Figeys, D., and Avruch, J. (2002) Death-associated protein 4 binds MST1 and aug-ments MST1-induced apoptosis. J. Biol. Chem. 277, 47991-48001 (Pubitemid 35470744)
118. Cinar, B., Fang, P.K., Lutchman, M., Di Vizio, D., Adam, R.M., Pavlova, N., Rubin, M.A., Yelick, P.C., and Freeman, M.R. (2007) The pro-apoptotic kinase Mst1 and its caspase cleavage products are direct inhibi-tors of Akt1. EMBO J. 26, 4523-4534 (Pubitemid 350036629)
119. Dallol, A., Hesson, L.B., Matallanas, D., Cooper, W.N., O'Neill, E., Maher, E.R., Kolch, W., and Latif, F. (2009) RAN GTPase is a RASSF1A effector involved in controlling microtubule organization. Curr. Biol. 19, 1227-1232
120. Zhou, D., Conrad, C., Xia, F., Park, J.S., Payer, B., Yin, Y., Lauwers, G.Y., Thasler, W., Lee, J.T., Avruch, J., and Bardeesy, N. (2009) Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocel-lular carcinoma development through inactivation of the Yap1 oncogene. Cancer Cell 16, 425-438
121. O'Neill, E., Rushworth, L., Baccarini, M., and Kolch, W. (2004) Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1. Science 306, 2267-2270 (Pubitemid 40024466)
122. Matallanas, D., Romano, D., Yee, K., Meissl, K., Kucerova, L., Piazzolla, D., Baccarini, M., Vass, J.K., Kolch, W., and O'Neill, E. (2007) RASSF1A elicits apoptosis through an MST2 pathway directing proa-poptotic transcription by the p73 tumor suppressor protein. Mol. Cell 27, 962-975 (Pubitemid 47495894)
123. Bi, W., Xiao, L., Jia, Y., Wu, J., Xie, Q., Ren, J., Ji, G., and Yuan, Z. (2010) c-Jun N-terminal kinase enhances MST1-mediated pro-apoptotic signaling through phos-phorylation at serine 82. J. Biol. Chem. 285, 6259-6264
124. Staley, B.K. and Irvine, K.D. (2010) Warts and Yorkie mediate intestinal regeneration by influencing stem cell proliferation. Curr. Biol. 20, 1580-1587
125. Jiang, H., Patel, P.H., Kohlmaier, A., Grenley, M.O., McEwen, D.G., and Edgar, B.A. (2009) Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell 137, 1343-1355
126. Karpowicz, P., Perez, J., and Perrimon, N. (2010) The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration. Development 137, 4135-4145
127. Hergovich, A., Cornils, H., and Hemmings, B.A. (2008) Mammalian NDR protein kinases: from regulation to a role in centrosome duplication. Biochim. Biophys. Acta 1784, 3-15
128. Geng, W., He, B., Wang, M., and Adler, P.N. (2000) The tricornered gene, which is required for the integrity of epidermal cell extensions, encodes the Drosophila nuclear DBF2-related kinase. Genetics 156, 1817-1828 (Pubitemid 32001244)
129. He, Y., Emoto, K., Fang, X., Ren, N., Tian, X., Jan, Y.N., and Adler, P.N. (2005) Drosophila Mob family proteins interact with the related tricornered (Trc) and warts (Wts) kinases. Mol. Biol. Cell 16, 4139-4152 (Pubitemid 41262884)
130. Emoto, K., Parrish, J.Z., Jan, L.Y., and Jan, Y.N. (2006) The tumour suppressor Hippo acts with the NDR kinases in dendritic tiling and maintenance. Nature 443, 210-213 (Pubitemid 44387608)
131. Vichalkovski, A., Gresko, E., Cornils, H., Hergovich, A., Schmitz, D., and Hemmings, B.A. (2008) NDR kinase is activated by RASSF1A/MST1 in response to Fas receptor stimulation and promotes apoptosis. Curr. Biol. 18, 1889-1895
132. Hergovich, A., Kohler, R.S., Schmitz, D., Vichalkovski, A., Cornils, H., and Hemmings, B.A. (2009) The MST1 and hMOB1 tumor suppressors control human centro-some duplication by regulating NDR kinase phosphor-ylation. Curr. Biol. 19, 1692-1702
133. Chiba, S., Ikeda, M., Katsunuma, K., Ohashi, K., and Mizuno, K. (2009) MST2-and Furry-mediated activa-tion of NDR1 kinase is critical for precise alignment of mitotic chromosomes. Curr. Biol. 19, 675-681
134. Cornils, H., Stegert, M.R., Hergovich, A., Hynx, D., Schmitz, D., Dirnhofer, S., and Hemmings, B.A. (2010) Ablation of the kinase NDR1 predisposes mice to the development of T cell lymphoma. Sci. Signal. 3, ra47
135. 2/M arrest or apoptosis. Oncogene 20, 6516-6523 (Pubitemid 32980276)
136. Xia, H., Qi, H., Li, Y., Pei, J., Barton, J., Blackstad, M., Xu, T., and Tao, W. (2002) LATS1 tumor suppressor regulates G2/M transition and apoptosis. Oncogene 21, 1233-1241 (Pubitemid 34185240)
137. Yabuta, N., Okada, N., Ito, A., Hosomi, T., Nishihara, S., Sasayama, Y., Fujimori, A., Okuzaki, D., Zhao, H., Ikawa, M., Okabe, M., and Nojima, H. (2007) Lats2 is an essential mitotic regulator required for the coordin-ation ofcell division. J. Biol. Chem. 282, 19259-19271 (Pubitemid 47100176)
138. Hirota, T., Morisaki, T., Nishiyama, Y., Marumoto, T., Tada, K., Hara, T., Masuko, N., Inagaki, M., Hatakeyama, K., and Saya, H. (2000) Zyxin: a regula-tor of actin filament assembly, targets the mitotic ap-paratus by interacting with h-warts/LATS1 tumor suppressor. J. Cell Biol. 149, 1073-1086 (Pubitemid 30354257)
139. Iida, S., Hirota, T., Morisaki, T., Marumoto, T., Hara, T., Kuninaka, S., Honda, S., Kosai, K., Kawasuji, M., Pallas, D.C., and Saya, H. (2004) Tumor suppressor WARTS ensures genomic integrity by regulating both mitotic progression and G1 tetraploidy checkpoint function. Oncogene 23, 5266-5274 (Pubitemid 39005802)
140. Li, Y., Pei, J., Xia, H., Ke, H., Wang, H., and Tao, W. (2003) Lats2, a putative tumor suppressor, inhibits G1/S transition. Oncogene 22, 4398-4405 (Pubitemid 36897970)
141. Toji, S., Yabuta, N., Hosomi, T., Nishihara, S., Kobayashi, T., Suzuki, S., Tamai, K., and Nojima, H. (2004) The centrosomal protein Lats2 is a phosphorylation target of Aurora-A kinase. Genes Cells 9, 383-397 (Pubitemid 38771930)
142. Abe, Y., Ohsugi, M., Haraguchi, K., Fujimoto, J., and Yamamoto, T. (2006) LATS2-Ajuba complex regulates γ-tubulin recruitment to centrosomes and spindle organization during mitosis. FEBS Lett. 580, 782-788 (Pubitemid 43152297)
143. Aylon, Y., Michael, D., Shmueli, A., Yabuta, N., Nojima, H., and Oren, M. (2006) A positive feedback loop between the p53 and Lats2 tumor suppressors pre-vents tetraploidization. Genes Dev. 20, 2687-2700 (Pubitemid 44498379)
144. Aylon, Y., Ofir-Rosenfeld, Y., Yabuta, N., Lapi, E., Nojima, H., Lu, X., and Oren, M. (2010) The Lats2 tumor suppressor augments p53-mediated apoptosis by promoting the nuclear proapoptotic function of ASPP1. Genes Dev. 24, 2420-2429
145. Vigneron, A.M., Ludwig, R.L., and Vousden, K.H. (2010) Cytoplasmic ASPP1 inhibits apoptosis through the control of YAP. Genes Dev. 24, 2430-2439
146. Voorhoeve, P.M., le Sage, C., Schrier, M., Gillis, A.J., Stoop, H., Nagel, R., Liu, Y.P., van Duijse, J., Drost, J., Griekspoor, A., Zlotorynski, E., Yabuta, N., De Vita, G., Nojima, H., Looijenga, L.H., and Agami, R. (2006) A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell 124, 1169-1181
147. Liu, X., Sempere, L.F., Ouyang, H., Memoli, V.A., Andrew, A.S., Luo, Y., Demidenko, E., Korc, M., Shi, W., Preis, M., Dragnev, K.H., Li, H., Direnzo, J., Bak, M., Freemantle, S.J., Kauppinen, S., and Dmitrovsky, E. (2010) MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors. J. Clin. Invest. 120, 1298-1309
148. Huntoon, C.J., Nye, M.D., Geng, L., Peterson, K.L., Flatten, K.S., Haluska, P., Kaufmann, S.H., and Karnitz, L.M. (2010) Heat shock protein 90 inhibition depletes LATS1 and LATS2, two regulators of the mammalian Hippo tumor suppressor pathway. Cancer Res. 70, 8642-8650
149. Van der Weyden, L. and Adams, D.J. (2007) The Ras-association domain family (RASSF) members and their role in human tumourigenesis. Biochim. Biophys. Acta 1776, 58-85 (Pubitemid 47332074)
150. Richter, A.M., Pfeifer, G.P., and Dammann, R.H. (2009) The RASSF proteins in cancer; from epigenetic silencing to functional characterization. Biochim. Biophys. Acta 1796, 114-128
151. Dammann, R., Li, C., Yoon, J.H., Chin, P.L., Bates, S., and Pfeifer, G.P. (2000) Epigenetic inactivation of a RAS association domain family protein from the lung tumor suppressor locus 3p21.3. Nat. Genet. 25, 315-319 (Pubitemid 30437320)
152. Tommasi, S., Dammann, R., Zhang, Z., Wang, Y., Liu, L., Tsark, W.M., Wilczynski, S.P., Li, J., You, M., and Pfeifer, G.P. (2005) Tumor susceptibility of Rassf1a knock-out mice. Cancer Res. 65, 92-98 (Pubitemid 40070799)
153. van der Weyden, L., Tachibana, K.K., Gonzalez, M.A., Adams, D.J., Ng, B.L., Petty, R., Venkitaraman, A.R., Arends, M.J., and Bradley, A. (2005) The RASSF1A isoform of RASSF1 promotes microtubule stability and suppresses tumorigenesis. Mol. Cell. Biol. 25, 8356-8367 (Pubitemid 41263023)
154. Vavvas, D., Li, X., Avruch, J., and Zhang, X.F. (1998) Identification of Nore1 as a potential Ras effector. J. Biol. Chem. 273, 5439-5442 (Pubitemid 28124004)
155. Khokhlatchev, A., Rabizadeh, S., Xavier, R., Nedwidek, M., Chen, T., Zhang, X.F., Seed, B., and Avruch, J. (2002) Identification of a novel Ras-regulated proapoptotic pathway. Curr. Biol. 12, 253-265 (Pubitemid 34161469)
156. Praskova, M., Khoklatchev, A., Ortiz-Vega, S., and Avruch, J. (2004) Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory pro-teins, RASSF1 and NORE1, and by Ras. Biochem. J. 381, 453-462 (Pubitemid 38969690)
157. Oh, H.J., Lee, K.K., Song, S.J., Jin, S.J., Song, M.S., Lee, J.H., Im, C.R., Lee, J.O., Yonehara, S., and Lim, D.S. (2006) Role of the tumor suppressor RASSF1A in Mst1-mediated apoptosis. Cancer Res. 66, 2562-2569
158. Guo, C., Tommasi, S., Liu, L., Yee, J.K., Dammann, R., and Pfeifer, G.P. (2007) RASSF1A is part of a com-plex similar to the Drosophila Hippo/Salvador/Lats tumor-suppressor network. Curr. Biol. 17, 700-705 (Pubitemid 46552245)
159. Hamilton, G., Yee, K.S., Scrace, S., and O'Neill, E. (2009) ATM regulates a RASSF1A-dependent DNA damage response. Curr. Biol. 19, 2020-2025
160. Ikeda, M., Hirabayashi, S., Fujiwara, N., Mori, H., Kawata, A., Iida, J., Bao, Y., Sato, Y., Iida, T., Sugimura, H., and Hata, Y. (2007) Ras-association domain family protein 6 induces apoptosis via both caspase-dependent and caspase-independent pathways. Exp. Cell Res. 313, 1484-1495 (Pubitemid 46507453)
161. Allen, N.P., Donninger, H., Vos, M.D., Eckfeld, K., Hesson, L., Gordon, L., Birrer, M.J., Latif, F., and Clark, G.J. (2007) RASSF6 is a novel member of the RASSF family of tumor suppressors. Oncogene 26, 6203-6211 (Pubitemid 47414375)
162. Ikeda, M., Kawata, A., Nishikawa, M., Tateishi, Y., Yamaguchi, M., Nakagawa, K., Hirabayashi, S., Bao, Y., Hidaka, S., Hirata, Y., and Hata, Y. (2009) Hippo pathway-dependent and-independent roles of RASSF6. Sci. Signal. 2, ra59
163. Baksh, S., Tommasi, S., Fenton, S., Yu, V.C., Martins, L.M., Pfeifer, G.P., Latif, F., Downward, J., and Neel, B.G. (2005) The tumor suppressor RASSF1A and MAP-1 link death receptor signaling to Bax conform-ational change and cell death. Mol. Cell 18, 637-650 (Pubitemid 40804800)
164. Vos, M.D., Dallol, A., Eckfeld, K., Allen, N.P., Donninger, H., Hesson, L.B., Calvisi, D., Latif, F., and Clark, G.J. (2006) The RASSF1A tumor sup-pressor activates Bax via MOAP-1. J. Biol. Chem. 281, 4557-4563 (Pubitemid 43847713)
165. Liu, L., Tommasi, S., Lee, D.H., Dammann, R., and Pfeifer, G.P. (2003) Control of microtubule stability by the RASSF1A tumor suppressor. Oncogene 22, 8125-8136 (Pubitemid 37487303)
166. Dallol, A., Agathanggelou, A., Fenton, S.L., Ahmed-Choudhury, J., Hesson, L., Vos, M.D., Clark, G.J., Downward, J., Maher, E.R., and Latif, F. (2004) RASSF1A interacts with microtubule-associated pro-teins and modulates microtubule dynamics. Cancer Res. 64, 4112-4116 (Pubitemid 38802412)
167. Song, M.S., Song, S.J., Ayad, N.G., Chang, J.S., Lee, J.H., Hong, H.K., Lee, H., Choi, N., Kim, J, Kim, H., Kim, J.W., Choi, E.J., Kirschner, M.W., and Lim, D.S. (2004) The tumour suppressor RASSF1A regulates mi-tosis by inhibiting the APC-Cdc20 complex. Nat. Cell Biol. 6, 129-137 (Pubitemid 38425712)
168. Rong, R., Jiang, L.Y., Sheikh, M.S., and Huang, Y. (2007) Mitotic kinase Aurora-A phosphorylates RASSF1A and modulates RASSF1A-mediatetd micro-tubule interaction and M-phase cell cycle regulation. Oncogene 26, 7700-7708 (Pubitemid 350224218)
169. Song, S.J., Song, M.S., Kim, S.J., Kim, S.Y., Kwon, S.H., Kim, J.G., Calvisi, D.F., Kang, D., and Lim, D.S. (2009) Aurora A regulates prometaphase progres-sion by inhibiting the ability of RASSF1A to suppress APC-Cdc20 activity. Cancer Res. 69, 2314-2323
170. Song, S.J., Kim, S.J., Song, M.S., and Lim, D.S. (2009) Aurora B-mediated phosphorylation of RASSF1A maintains proper cytokinesis by recruiting Syntaxin16 to the midzone and midbody. Cancer Res. 69, 8540-8544
171. Song, M.S., Song, S.J., Kim, S.Y., Oh, H.J., and Lim, D.S. (2008) The tumour suppressor RASSF1A pro-motes MDM2 self-ubiquitination by disrupting the MDM2-DAXX-HAUSP complex. EMBO J. 27, 1863-1874
172. Song, M.S., Song, S.J., Kim, S.J., Nakayama, K., Nakayama, K.I., and Lim, D.S. (2008) Skp2 regulates the antiproliferative function of the tumor suppressor RASSF1A via ubiquitin-mediated degradation at the G1-S transition. Oncogene 27, 3176-3185 (Pubitemid 351693166)
173. Kitagawa, D., Kajiho, H., Negishi, T., Ura, S., Watanabe, T., Wada, T., Ichijo, H., Katada, T., and Nishina, H. (2006) Release of RASSF1C from the nu-cleus by Daxx degradation links DNA damage and SAPK/JNK activation. EMBO J. 25, 3286-3297 (Pubitemid 44141787)
174. Wang, K., Degerny, C., Xu, M., and Yang, X.J. (2009) YAP, TAZ, and Yorkie:a conserved family of signal-responsive transcriptional coregulators in animal devel-opment and human disease. Biochem. Cell Biol. 87, 77-91
175. Oh, H. and Irvine, K.D. (2010) Yorkie: the final destin-ation ofHippo signaling. Trends CellBiol. 20, 410-417
176. Hong, J.H. and Yaffe, M.B. (2006) TAZ: a beta-catenin-like molecule that regulates mesenchymal stem cell differentiation. Cell Cycle 5, 176-179 (Pubitemid 43131155)
177. Downward, J. and Basu, S. (2008) YAP and p73: a complex affair. Mol. Cell 32, 749-750
178. Zhang, X., Milton, C.C., Humbert, P.O., and Harvey, K.H. (2009) Transcriptional output of the Salvador/warts/hippo pathway is controlled in distinct fashions in Drosophila melanogaster and mammalian cell lines. Cancer Res. 69, 6033-6041
179. Basu, S., Totty, N.F., Irwin, M.S., Sudol, M., and Downward, J. (2003) Akt phosphorylates the Yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation ofp73-mediated apoptosis. Mol. Cell 11, 11-23 (Pubitemid 36126587)
180. Yuan, M., Tomlinson, V., Lara, R., Holliday, D., Chelala, C., Harada, T., Gangeswaran, R., Manson-Bishop, C., Smith, P., Danovi, S.A., Pardo, O., Crook, T., Mein, C.A., Lemoine, N.R., Jones, L.J., and Basu, S. (2008) Yes-associated protein (YAP) func-tions as a tumor suppressor in breast. Cell Death Differ. 15, 1752-1759
181. Lapi, E., Di Agostino, S., Donzelli, S., Gal, H., Domany, E., Rechavi, G., Pandolfi, P.P., Givol, D., Strano, S., Lu, X., and Blandino, G (2008) PML, YAP, and p73 are components of a proapoptotic auto-regulatory feedback loop. Mol. Cell32, 803-814
182. Levy, D., Adamovich, Y., Reuven, N., and Shaul, Y. (2007) The Yes-associated protein 1 stabilizes p73 by preventing Itch-mediated ubiquitination of p73. Cell Death Differ. 14, 743-751 (Pubitemid 46444512)
183. Levy, D., Adamovich, Y., Reuven, N., and Shaul, Y. (2008) Yap1 phosphorylation by c-Abl is a critical step in selective activation of proapoptotic genes in response to DNA damage. Mol. Cell 29, 350-361 (Pubitemid 351215937)
184. Hoshino, M., Qi, M.L., Yoshimura, N., Miyashita, T., Tagawa, K., Wada, Y., Enokido, Y., Marubuchi, S., Harjes, P., Arai, N., Oyanagi, K., Blandino, G., Sudol, M., Rich, T., Kanazawa, I., Wanker, E.E., Saitoe, M., and Okazawa, H. (2006) Transcriptional re-pression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73. J. Cell Biol. 172, 589-604 (Pubitemid 43243879)
185. Remue, E., Meerschaert, K., Oka, T., Boucherie, C., Vandekerckhove, J., Sudol, M., and Gettemans, J. (2010) TAZ interacts with zonula occludens-1 and-2 proteins in a PDZ-1 dependent manner. FEBS Lett. 584, 4175-4180
186. Oka, T., Remue, E., Meerschaert, K., Vanloo, B., Boucherie, C., Gfeller, D., Bader, G.D., Sidhu, S.S., Vandekerckhove, J., Gettemans, J., and Sudol, M. (2010) Functional complexes between YAP2 and ZO-2 are PDZ domain-dependent, and regulate YAP2 nuclear localization and signaling. Biochem. J. 432, 461-472
187. Varelas, X., Samavarchi-Tehrani, P., Narimatsu, M., Weiss, A., Cockburn, K., Larsen, B.G., Rossant, J., and Wrana, J.L. (2010) The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-β-SMAD pathway. Dev. Cell 19, 831-844
188. Zhao, B., Li, L., Tumaneng, K., Wang, C.Y., and Guan, K.L. (2010) A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCFβ-TRCP Genes Dev 24, 72-85
189. -TrCP E3 ligase. J. Biol. Chem. 285, 37159-37169
190. Overholtzer, M., Zhang, J., Smolen, G.A., Muir, B., Li, W., Sgroi, D.C., Deng, C.X., Brugge, J.S., and Haber, D.A. (2006) Transforming properties of YAP, a candi-date oncogene on the chromosome 11q22 amplicon. Proc. Natl. Acad. Sci. USA 103, 12405-12410 (Pubitemid 44267272)
191. Zhao, B., Wei, X., Li, W., Udan, R.S., Yang, Q., Kim, J., Xie, J., Ikenoue, T., Yu, J., Li, L., Zheng, P., Ye, K., Chinnaiyan, A., Halder, G., Lai, Z.C., and Guan, K.L. (2007) Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev. 21, 2747-2761 (Pubitemid 350070721)
192. Lei, Q.Y., Zhang, H., Zhao, B., Zha, Z.Y., Bai, F., Pei, X.H., Zhao, S., Xiong, Y., and Guan, K.L. (2008) TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway. Mol. Cell. Biol. 28, 2426-2436 (Pubitemid 351429986)
193. Zhao, B., Ye, X., Yu, J., Li, L., Li, W., Li, S., Yu, J., Lin, J.D., Wang, C.Y., Chinnaiyan, A.M., Lai, Z.C., and Guan, K.L. (2008) TEAD mediates YAP-dependent gene induction and growth control. Genes Dev. 22, 1962-1971 (Pubitemid 352008643)
194. Zhang, H., Liu, C.Y., Zha, Z.Y., Zhao, B., Yao, J., Zhao, S., Xiong, Y., Lei, Q.Y., and Guan, K.L. (2009) TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition. J. Biol. Chem. 284, 13355-13362
195. Xu, M.Z., Chan, S.W., Liu, A.M., Wong, K.F., Fan, S.T., Chen, J., Poon, R.T., Zender, L., Lowe, S.W., Hong, W., and Luk, J.M. (2011) AXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinoma. Oncogene 30, 1229-1240
196. Chan, S.W., Lim, C.J., Huang, C., Chong, Y.F., Gunaratne, H.J., Hogue, K.A., Blackstock, W.P., Harvey, K.F., and Hong, W. (2011) WW domain-mediated interaction with Wbp2 is important for the oncogenic property ofTAZ. Oncogene 30, 600-610
197. McNeill, H. and Woodgett, J.R. (2010) When pathways collide: collaboration and connivance among signalling proteins in development. Nat. Rev. Mol. Cell. Biol. 11, 404-413
198. Neto-Silva, R.M., de Beco, S., and Johnston, L.A. (2010) Evidence for a growth-stabilizing regulatory feedback mechanism between Myc and Yorkie, the Drosophila homolog of Yap. Dev. Cell 19, 507-520
199. Ziosi, M., Baena-Lopez, L.A., Grifoni, D., Froldi, F., Pession, A., Garoia, F., Trotta, V., Bellosta, P., Cavicchi, S., and Pession, A. (2010) dMyc functions downstream of Yorkie to promote the supercompetitive behavior ofhippo pathway mutant cells. PLoS Genet. 6, e1001140
200. Polesello, C. and Tapon, N. (2007) Salvador-warts-hippo signaling promotes Drosophila posterior follicle cell maturation downstream of notch. Curr. Biol. 17, 1864-1870 (Pubitemid 350016921)
201. Meignin, C., Alvarez-Garcia, I., Davis, I., and Palacios, I.M. (2007) The salvador-warts-hippo pathway is required for epithelial proliferation and axis specifica-tion in Drosophila. Curr. Biol. 17, 1871-1878 (Pubitemid 350016928)
202. Yu, J., Poulton, J., Huang, Y.C., and Deng, W.M. (2008) The hippo pathway promotes Notch signaling in regulation of cell differentiation, proliferation, and oocyte polarity. PLoS ONE 3, e1761
203. Reddy, B.V., Rauskolb, C., and Irvine, K.D. (2010) Influence of fat-hippo and notch signaling on the proliferation and differentiation of Drosophila optic neuroepithelia. Development 137, 2397-2408
204. Camargo, F.D., Gokhale, S., Johnnidis, J.B., Fu, D., Bell, G.W., Jaenisch, R., and Brummelkamp, T.R. (2007) YAP1 increases organ size and expands undiffer-entiated progenitor cells. Curr. Biol. 17, 2054-2060 (Pubitemid 350180465)
205. Varelas, X., Miller, B.W., Sopko, R., Song, S., Gregorieff, A., Fellouse, F.A., Sakuma, R., Pawson, T., Hunziker, W., McNeill, H., Wrana, J.L., and Attisano, L. (2010) The Hippo pathway regulates Wnt/β-catenin signaling. Dev. Cell 18, 579-591
206. Alarcon, C., Zaromytidou, A.I., Xi, Q., Gao, S., Yu, J., Fujisawa, S., Barlas, A., Miller, A.N., Manova-Todorova, K., Macias, M.J., Sapkota, G., Pan, D., and Massague, J. (2009) Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-β pathways. Cell 139, 757-769
207. Varelas, X., Sakuma, R., Samavarchi-Tehrani, P., Peerani, R., Rao, B.M., Dembowy, J., Yaffe, M.B., Zandstra, P.W., and Wrana, J.L. (2008) TAZ controls Smad nuleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal. Nat. Cell Biol. 10, 837-848 (Pubitemid 351927712)
208. Fernandez-L.A., Northcott, P.A., Dalton, J., Fraga, C., Ellison, D., Angers, S., Taylor, M.D., and Kenney, A.M. (2009) YAP1 is amplified and up-regulated in hedgehog-associated medulloblastomas and mediates Sonic hedgehog-driven neural precursor proliferation. Genes Dev. 23, 2729-2741
209. Zhang, J., Ji, J.Y., Yu, M., Overholtzer, M., Smolen, G.A., Wang, R., Brugge, J.S., Dyson, N.J., and Haber, D.A. (2009) YAP-dependent induction of amphiregulin identifies a non-cell-autonomous component of the Hippo pathway. Nat. CellBiol. 11, 1444-1450
210. Nishioka, N., Inoue, K., Adachi, K., Kiyonari, H., Ota, M., Ralston, A., Yabuta, N., Hirahara, S., Stephenson, R.O., Ogonuki, N., Makita, R., Kurihara, H., Morin-Kensicki, E.M., Nojima, H., Rossant, J., Nakao, K., Niwa, H., and Sasaki, H. (2009) The Hippo signaling pathway components Lats and Yap pattern Tead4 ac-tivity to distinguish mouse trophectoderm from inner cell mass. Dev. Cell 16, 398-410
211. McClatchey, A.I., Saotome, I., Ramesh, V., Gusella, J.F., and Jacks, T. (1997) The Nf2 tumor suppressor gene product is essential for extraembryonic develop-ment immediately prior to gastrulation. Genes Dev. 11, 1253-1265 (Pubitemid 27235358)
212. Saburi, S., Hester, I., Fisher, E., Pontoglio, M., Eremina, V., Gessler, M., Quaggin, S.E., Harrison, R., Mount, R., and McNeill, H. (2008) Loss of Fat4 dis-rupts PCP signaling and oriented cell division and leads to cystic kidney disease. Nat. Genet. 40, 1010-1015
213. Lee, J.H., Kim, T.S., Yang, T.H., Koo, B.K., Oh, S.P., Lee, K.P., Oh, H.J., Lee, S.H., Kong, Y.Y., Kim, J.M., and Lim, D.S. (2008) A crucial role of WW45 in de-veloping epithelial tissues in the mouse. EMBO J. 27, 1231-1242
214. Oh, S., Lee, D., Kim, T., Kim, T.S., Oh, H.J., Hwang, C.Y., Kong, Y.Y., Kwon, K.S., and Lim, D.S. (2009) Crucial role for Mst1 and Mst2 kinases in early embry-onic development of the mouse. Mol. Cell. Biol. 29, 6309-6320
215. St John, M.A., Tao, W., Fei, X., Fukumoto, R., Carcangiu, M.L., Brownstein, D.G., Parlow, A.F., McGrath, J., and Xu, T. (1999) Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction. Nat. Genet. 21, 182-186 (Pubitemid 29070363)
216. McPherson, J.P., Tamblyn, L., Elia, A., Migon, E., Shehabeldin, A., Matysiak-Zablocki, E., Lemmers, B., Salmena, L., Hakem, A., Fish, J., Kassam, F., Squire, J., Bruneau, B.G., Hande, M.P., and Hakem, R. (2004) Lats2/Kpm is required for embryonic development, proliferation control and genomic integrity. EMBO J. 23, 3677-3688 (Pubitemid 39336289)
217. Morin-Kensicki, E.M., Boone, B.N., Howell, M., Stonebraker, J.R., Teed, J., Alb, J.G., Magnuson, T.R., O'Neal, W., and Milgram, S.L. (2006) Defects of yolk sac vasculogenesis, chorioallantoic fusion, and embryonic axis elongation in mice with targeted disrup-tion of Yap65. Mol. Cell. Biol. 26, 77-87
218. Hossain, Z., Ali, S.M., Ko, H.L., Xu, J., Ng, C.P., Guo, K., Qi, Z., Ponniah, S., Hong, W., and Hunziker, W. (2007) Glomerulocystic kidney disease in mice with a targeted inactivation ofWwtr1. Proc. Natl. Acad. Sci. USA 104, 1631-1636 (Pubitemid 46214642)
219. Makita, R., Uchijima, Y., Nishiyama, K., Amano, T., Chen, Q., Takeuchi, T., Mitani, A., Nagase, T., Yatomi, Y., Aburatani, H., Nakagawa, O., Small, E.V., Cobo-Stark, P., Igarashi, P., Murakami, M., Tominaga, J., Sato, T., Asano, T., Kurihara, Y., and Kurihara, H. (2008) Multiple renal cysts, urinary concentration defects, and pulmonary emphysematous changes in mice lacking TAZ. Am. J. Physiol. Renal Physiol. 294, F542-F553 (Pubitemid 351442224)
220. McClatchey, A.I., Saotome, I., Mercer, K., Crowley, D., Gusella, J.F., Bronson, R.T., and Jacks, T. (1998) Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors. GenesDev. 12, 1121-1133 (Pubitemid 28194048)
221. Giovannini, M., Robanus-Maandag, E., van der Valk, M., Niwa-Kawakita, M., Abramowski, V., Goutebroze, L., Woodruff, J.M., Berns, A., and Thomas, G (2000) Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2. Genes Dev. 14, 1617-1630 (Pubitemid 30460911)
222. Lee, K.P., Lee, J.H., Kim, T.S., Kim, T.H., Park, H.D., Byun, J.S., Kim, M.C., Jeong, W.I., Calvisi, D.F., Kim, J.M., and Lim, D.S. (2010) The Hippo-Salvador path-way restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis. Proc. Natl. Acad. Sci. USA 107, 8248-8253
223. Song, H., Mak, K.K., Topol, L., Yun, K., Hu, J., Garrett, L., Chen, Y., Park, O., Chang, J., Simpson, R.M., Wang, C.Y., Gao, B., Jiang, J., and Yang, Y. (2010) Mammalian Mst1 and Mst2 kinases play essen-tial roles in organ size control and tumor suppression. Proc. Natl. Acad. Sci. USA 107, 1431-1436
224. Lu, L., Li, Y., Kim, S.M., Bossuyt, W., Liu, P., Qiu, Q., Wang, Y., Halder, G., Finegold, M.J., Lee, J.S., and Johnson, R.L. (2010) Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver. Proc. Natl. Acad. Sci. USA 107, 1437-1442
225. Avruch, J., Zhou, D., Pitamant, J., and Bardeesy, N. (2010) Mst1/2 signaling to Yap: gatekeeper for liver size and tumor development. Br. J. Cancer 104, 24-32
226. Odashima, M., Usui, S., Takagi, H., Hong, C., Liu, J., Yokota, M., and Sadoshima, J. (2007) Inhibition of en-dogenous Mst1 prevents apoptosis and cardiac dysfunc-tion without affecting cardiac hypertrophy after myocardial infarction. Circ. Res. 100, 1344-1352 (Pubitemid 46742925)
227. Matsui, Y., Nakano, N., Shao, D., Gao, S., Luo, W., Hong, C., Zhai, P., Holle, E., Yu, X., Yabuta, N., Tao, W., Wagner, T., Nojima, H., and Sadoshima, J. (2008) Lats2 is a negative regulator of myocyte size in the heart. Circ. Res. 103, 1309-1318
228. Oceandy, D., Pickard, A., Prehar, S., Zi, M., Mohamed, T.M., Stanley, P.J., Baudoin-Stanley, F., Nadif, R., Tommasi, S., Pfeifer, G.P., Armesilla, A.L., Cartwright, E.J., and Neyses, L. (2009) Tumor suppres-sor Ras-association domain family 1 isoform A is a novel regulator of cardiac hypertrophy. Circulation 120, 607-616
229. Del Re, D.P., Matsuda, T., Zhai, P., Gao, S., Clark, G.J., van der Weyden, L., and Sadoshima, J. (2010) Proapoptotic Rassf1A/Mst1 signaling in cardiac fibro-blasts is protective against pressure overload in mice. J. Clin. Invest. 120, 3555-3567
230. Cao, X., Pfaff, S.L., and Gage, F.H. (2008) YAP regu-lates neural progenitor cell number via the TEA domain transcription factor. Genes Dev. 22, 3320-3334
231. Hong, J.H., Hwang, E.S., McManus, M.T., Amsterdam, A., Tian, Y., Kalmukova, R., Mueller, E., Benjamin, T., Spiegelman, B.M., Sharp, P.A., Hopkins, N., and Yaffe, M.B. (2005) TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science 309, 1074-1078 (Pubitemid 41134465)
232. Zaidi, S.K., Sullivan, A.J., Medina, R., Ito, Y., van Wijnen, A.J., Stein, J.L., Lian, J.B., and Stein, G.S. (2004) Tyrosine phosphorylation controls Runx2-mediated subnuclear targeting of YAP to repress tran-scription. EMBO J. 23, 790-799 (Pubitemid 38418746)
233. Jeong, H., Bae, S., An, S.Y., Byun, M.R., Hwang, J.H., Yaffe, M.B., Hong, J.H., and Hwang, E.S. (2010) TAZ as a novel enhancer of MyoD-mediated myogenic dif-ferentiation. FASEB J. 24, 3310-3320
234. Watt, K.I., Judson, R., Medlow, P., Reid, K., Kurth, T.B., Burniston, J.G., Ratkevicius, A., De Bari, C., and Wackerhage, H. (2010) Yap is a novel regulator of C2C12 myogenesis. Biochem. Biophys. Res. Commun. 393, 619-624
235. Lian, I., Kim, J., Okazawa, H., Zhao, J., Zhao, B., Yu, J., Chinnaiyan, A., Israel, M.A., Goldstein, L.S., Abujarour, R., Ding, S., and Guan, K.L. (2010) The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiation. Genes Dev. 24, 1106-1118
236. Staley, B.K and Irvine, K.D. (2010) Warts and Yorkie mediate intestinal regeneration by influencing stem cell proliferation. Curr. Biol. 20, 1580-1587
237. Shaw, R.L., Kohlmaier, A., Polesello, C., Veelken, C., Edgar, B.A., and Tapon, N. (2010) The Hippo pathway regulates intestinal stem cell proliferation during Drosophila adult midgut regeneration. Development 137, 4147-4158
238. Cai, J., Zhang, N., Zheng, Y., de Wilde, R.F., Maitra, A., and Pan, D. (2010) The Hippo signaling pathway restricts the oncogenic potential of an intestinal regen-eration program. Genes Dev. 24, 2383-2388
239. Katagiri, K., Imamura, M., and Kinashi, T. (2006) Spatiotemporal regulation of the kinase Mst1 by bind-ing protein RAPL is critical for lymphocyte polarity and adhesion. Nat. Immunol. 7, 919-928 (Pubitemid 44263905)
240. Katagiri, K., Katakai, T., Ebisuno, Y., Ueda, Y., Okada, T., and Kinashi, T. (2009) Mst1 controls lymphocyte trafficking and interstitial motility within lymph nodes. EMBO J. 28, 1319-1331
241. Dong, Y., Du, X., Ye, J., Han, M., Xu, T., Zhuang, Y., and Tao, W. (2009) A cell-intrinsic role for Mst1 in regulating thymocyte egress. J. Immunol. 183, 3865-3872
242. Zhou, D., Medoff, B.D., Chen, L., Li, L., Zhang, X.F., Praskova, M., Liu, M., Landry, A., Blumberg, R.S., Boussiotis, V.A., Xavier, R., and Avruch, J. (2008) The Nore1B/Mst1 complex restrains antigen receptor-induced proliferation ofnaive T cells. Proc. Natl. Acad. Sci. USA 195, 20321-20326
243. Hansson, C.M., Buckley, P.G., Grigelioniene, G., Piotrowski, A., Hellstrom, A.R., Mantripragada, K., Jarbo, C., Mathiesen, T., and Dumanski, J.P. (2007) Comprehensive genetic and epigenetic analysis of sporadic meningioma for macro-mutations on 22q and micro-mutations within NF2 locus. BMC Genomics 8, 16
244. Sekido, Y. (2010) Genomic abnormalities and signal transduction dysregulation in malignant mesothelioma cells. Cancer Sci. 101, 1-6
245. Jiang, Z., Li, X., Hu, J., Zhou, W., Jiang, Y., Li, G., and Lu, D. (2006) Promoter hypermethylation-mediated down-regulation ofLATS1 and LATS2 in human astro-cytoma. Neurosci. Res. 56, 450-458 (Pubitemid 44750270)
246. Takahashi, Y., Miyoshi, Y., Takahara, C., Irahara, N., Taguchi, T., Tamaki, Y., and Noguchi, S. (2005) Down-regulation of LATS1 and LATS2 mRNA expres-sion by promoter hypermethylation and its association with biologically aggressive phenotype in human breast cancers. Clin. Cancer Res. 11, 1380-1385 (Pubitemid 40315216)
247. Seidel, C., Schagdarsurengin, U., Blumke, K., Wurl, P., Pfeifer, G.P., Hauptmann, S., Taubert, H., and Dammann, R. (2007) Frequent hypermethylation of MST1 and MST2 in soft tissue sarcoma. Mol. Carcinog. 46, 865-871 (Pubitemid 47549772)
248. Hesson, L.B., Dunwell, T.L., Cooper, W.N., Catchpoole, D., Brini, A.T., Chiaramonte, R., Griffiths, M., Chalmers, A.D., Maher, E.R., and Latif, F. (2009) The novel RASSF6 and RASSF10 candidate tumour suppressor genes are frequently epigenetically inactivated in childhood leukaemias. Mol. Cancer 8, 42
249. Steinhardt, A.A., Gayyed, M.F., Klein, A.P., Dong, J., Maitra, A., Pan, D., Montgomery, E.A., and Anders, R.A. (2008) Expression of Yes-associated protein in common solid tumors. Hum. Pathol. 39, 1582-1589
250. Minoo, P., Zlobec, I., Baker, K., Tornillo, L., Terracciano, L., Jass, J.R., and Lugli, A. (2007) Prognostic significance of mammalian sterile20-like kinase 1 in colorectal cancer. Mod. Pathol. 20, 331-338 (Pubitemid 46348330)
251. Xu, M.Z., Yao, T.J, Lee, N.P., Ng, I.O., Chan, Y.T., Zender, L., Lowe, S.W., Poon, R.T., and Luk, J.M. (2009) Yes-associated protein is an independent prog-nostic marker in hepatocellular carcinoma. Cancer 115, 4576-4585
252. Kalluri, R. and Weinberg, R.A. (2009) The basics of epithelial- mesenchymal transition. J. Clin. Invest. 119, 1420-1428
253. Zhao, B., Li, L., Lu, Q., Wang, L.H., Liu, C.Y., Lei, Q., and Guan, K.H. (2011) Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein. Genes Dev. 25, 51-63
254. Wang, W., Huang, J., and Chen, J. (2011) Angiomotin-like proteins associate with and negatively regulate YAP1. J. Biol. Chem. 286, 4364-4370
255. Chan, S.W., Lim, C.J., Chong, Y.F., Pobbati, A.V., Huang, C., and Hong, W. (2011) Hippo pathway-independent restriction of TAZ and YAP by angiomo-tin. J. Biol. Chem. 286, 7018-7926