Integrin signalling regulates YAP and TAZ to control skin homeostasis

Development (Cambridge)

Volumn 143, Issue 10, 2016, Pages 1674-1687

  Elbediwy, Ahmed ^a   Vincent Mistiaen, Zoé I ^a   Spencer Dene, Bradley ^a   Stone, Richard K ^a   Boeing, Stefan ^a   Wculek, Stefanie K ^a   Cordero, Julia ^b   Tan, Ee H ^b   Ridgway, Rachel ^c   Brunton, Val G ^c   Sahai, Erik ^a   Gerhardt, Holger ^a   Behrens, Axel ^a   Malanchi, Ilaria ^a   Sansom, Owen J ^b   Thompson, Barry J ^a  

^a THE FRANCIS CRICK INSTITUTE   (United Kingdom)

^b BEATSON INSTITUTE FOR CANCER RESEARCH   (United Kingdom)

^c UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

Hippo pathway; Integrin; Stratified squamous epithelium; TAZ; Yes associated protein

Indexed keywords

CRB3 PROTEIN; DASATINIB; DROSOPHILA PROTEIN; HIPPO PROTEIN; INTEGRIN; KIBRA PROTEIN; MEMBRANE PROTEIN; MERLIN; SAV1 PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR TAZ; TRANSCRIPTION FACTOR YAP; UNCLASSIFIED DRUG; EPIDERMAL GROWTH FACTOR RECEPTOR; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHOPROTEIN; PROTEIN TYROSINE KINASE; SIGNAL PEPTIDE; SIGNAL TRANSDUCING ADAPTOR PROTEIN; WWTR1 PROTEIN, HUMAN; WWTR1 PROTEIN, MOUSE; YAP PROTEIN, MOUSE; YAP1 (YES-ASSOCIATED) PROTEIN, HUMAN;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; BASEMENT MEMBRANE; CELL CONTACT; CELL DIFFERENTIATION; CELL NUCLEUS; CELL PROLIFERATION; CELL REGENERATION; CHEMOSENSITIVITY; CONTROLLED STUDY; CYTOPLASM; DAUGHTER CELL; EPITHELIUM TUMOR; EXTRACELLULAR MATRIX; GENE EXPRESSION; HAIR LOSS; HOMEOSTASIS; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN LOCALIZATION; SIGNAL TRANSDUCTION; SKIN; SKIN CARCINOGENESIS; SKIN CARCINOMA; SKIN HOMEOSTASIS; SKIN PAPILLOMA; SQUAMOUS CELL CARCINOMA; TUMOR GROWTH; WOUND HEALING; ANIMAL; CELL LINE; CYTOLOGY; DRUG EFFECTS; EPITHELIUM; GENE EXPRESSION REGULATION; GENETICS; KERATINOCYTE; METABOLISM; PATHOLOGY; PROTEIN STABILITY; PROTEIN TRANSPORT; STEM CELL;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANIMALS; CELL DIFFERENTIATION; CELL LINE; CELL NUCLEUS; DASATINIB; EPITHELIUM; GENE EXPRESSION REGULATION; HOMEOSTASIS; HUMANS; INTEGRINS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; KERATINOCYTES; MICE; NEOPLASMS, SQUAMOUS CELL; PHOSPHATIDYLINOSITOL 3-KINASES; PHOSPHOPROTEINS; PROTEIN STABILITY; PROTEIN TRANSPORT; RECEPTOR, EPIDERMAL GROWTH FACTOR; SIGNAL TRANSDUCTION; SKIN; SRC-FAMILY KINASES; STEM CELLS; WOUND HEALING;

EID: 84968861346     PISSN: 09501991     EISSN: 14779129     Source Type: Journal    
DOI: 10.1242/dev.133728     Document Type: Article

References (109)

1. Akhtar, N. and Streuli, C. H. (2013). An integrin-ILK-microtubule network orients cell polarity and lumen formation in glandular epithelium. Nat. Cell Biol. 15, 17-27.
2. Anani, S., Bhat, S., Honma-Yamanaka, N., Krawchuk, D. and Yamanaka, Y. (2014). Initiation of Hippo signaling is linked to polarity rather than to cell position in the pre-implantation mouse embryo. Development 141, 2813-2824.
3. Aragona, M., Panciera, T., Manfrin, A., Giulitti, S., Michielin, F., Elvassore, N., Dupont, S. and Piccolo, S. (2013). A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors. Cell 154, 1047-1059.
4. Azzolin, L., Panciera, T., Soligo, S., Enzo, E., Bicciato, S., Dupont, S., Bresolin, S., Frasson, C., Basso, G., Guzzardo, V. et al. (2014). YAP/TAZ incorporation in the beta-catenin destruction complex orchestrates the Wnt response. Cell 158, 157-170.
5. Baumgartner, R., Poernbacher, I., Buser, N., Hafen, E. and Stocker, H. (2010). TheWWdomain protein Kibra acts upstream of Hippo in Drosophila. Dev. Cell 18, 309-316.
6. Benham-Pyle, B. W., Pruitt, B. L. and Nelson, W. J. (2015). Cell adhesion. Mechanical strain induces E-cadherin-dependent Yap1 and beta-catenin activation to drive cell cycle entry. Science 348, 1024-1027.
7. Berglund, L., Bjorling, E., Oksvold, P., Fagerberg, L., Asplund, A., Szigyarto, C. A.-K., Persson, A., Ottosson, J., Wernerus, H., Nilsson, P. et al. (2008). A genecentric Human Protein Atlas for expression profiles based on antibodies. Mol. Cell. Proteomics 7, 2019-2027.
8. Brakebusch, C., Grose, R.,Quondamatteo, F., Ramirez, A., Jorcano, J. L., Pirro, A., Svensson, M., Herken, R., Sasaki, T., Timpl, R. et al. (2000). Skin and hair follicle integrity is crucially dependent on beta 1 integrin expression on keratinocytes. EMBO J. 19, 3990-4003.
9. Bryant, D. M., Roignot, J., Datta, A., Overeem, A. W., Kim, M., Yu, W., Peng, X., Eastburn, D. J., Ewald, A. J., Werb, Z. et al. (2014). A molecular switch for the orientation of epithelial cell polarization. Dev. Cell 31, 171-187.
10. 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 regeneration program. Genes Dev. 24, 2383-2388.
11. Cai, J., Maitra, A., Anders, R. A., Taketo, M. M. and Pan, D. (2015). beta-Catenin destruction complex-independent regulation of Hippo-YAP signaling by APC in intestinal tumorigenesis. Genes Dev. 29, 1493-1506.
12. 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 undifferentiated progenitor cells. Curr. Biol. 17, 2054-2060.
13. 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.
14. 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.
15. Cordero, J. B., Ridgway, R. A., Valeri, N., Nixon, C., Frame, M. C., Muller, W. J., Vidal, M. and Sansom, O. J. (2014). c-Src drives intestinal regeneration and transformation. EMBO J. 33, 1474-1491.
16. Creedon, H. and Brunton, V. G. (2012). Src kinase inhibitors: promising cancer therapeutics? Crit. Rev. Oncog. 17, 145-159.
17. 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 signaling pathway. Curr. Biol. 20, 657-662.
18. Degoutin, J. L., Milton, C. C., Yu, E., Tipping, M., Bosveld, F., Yang, L., Bellaiche, Y., Veraksa, A. and Harvey, K. F. (2013). Riquiqui and minibrain are regulators of the Hippo pathway downstream of Dachsous. Nat. Cell Biol. 15, 1176-1185.
19. Doggett, K., Grusche, F. A., Richardson, H. E. and Brumby, A. M. (2011). Loss of the Drosophila cell polarity regulator Scribbled promotes epithelial tissue overgrowth and cooperation with oncogenic Ras-Raf through impaired Hippo pathway signaling. BMC Dev. Biol. 11, 57.
20. 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.
21. Dupont, S., Morsut, L., Aragona, M., Enzo, E., Giulitti, S., Cordenonsi, M., Zanconato, F., Le Digabel, J., Forcato, M., Bicciato, S. et al. (2011). Role of YAP/TAZ in mechanotransduction. Nature 474, 179-183.
22. Elbediwy, A., Zihni, C., Terry, S. J., Clark, P., Matter, K. and Balda, M. S. (2012). Epithelial junction formation requires confinement of Cdc42 activity by a novel SH3BP1 complex. J. Cell Biol. 198, 677-693.
23. Enomoto, M. and Igaki, T. (2013). Src controls tumorigenesis via JNK-dependent regulation of the Hippo pathway in Drosophila. EMBO Rep. 14, 65-72.
24. Fan, R., Kim, N.-G. and Gumbiner, B. M. (2013). Regulation of Hippo pathway by mitogenic growth factors via phosphoinositide 3-kinase and phosphoinositidedependent kinase-1. Proc. Natl. Acad. Sci. USA 110, 2569-2574.
25. Fernandez, B. G., Gaspar, P., Bras-Pereira, C., Jezowska, B., Rebelo, S. R. and Janody, F. (2011). Actin-Capping Protein and the Hippo pathway regulate F-actin and tissue growth in Drosophila. Development 138, 2337-2346.
26. Fernandez, B. G., Jezowska, B. and Janody, F. (2014). Drosophila actin-Capping Protein limits JNK activation by the Src proto-oncogene. Oncogene 33, 2027-2039.
27. Fletcher, G. C., Lucas, E. P., Brain, R., Tournier, A. and Thompson, B. J. (2012). Positive feedback and mutual antagonism combine to polarize Crumbs in the Drosophila follicle cell epithelium. Curr. Biol. 22, 1116-1122.
28. Fletcher, G. C., Elbediwy, A., Khanal, I., Ribeiro, P. S., Tapon, N. and Thompson, B. J. (2015). The Spectrin cytoskeleton regulates the Hippo signalling pathway. EMBO J. 34, 940-954.
29. Gaspar, P., Holder, M. V., Aerne, B. L., Janody, F. and Tapon, N. (2015). Zyxin antagonizes the FERM protein expanded to couple F-actin and Yorkie-dependent organ growth. Curr. Biol. 25, 679-689.
30. 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.
31. Grose, R., Hutter, C., Bloch,W., Thorey, I., Watt, F. M., Fassler, R., Brakebusch, C. and Werner, S. (2002). A crucial role of beta 1 integrins for keratinocyte migration in vitro and during cutaneous wound repair. Development 129, 2303-2315.
32. 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 signalling to regulate cell proliferation and apoptosis. Nat. Cell Biol. 8, 27-36.
33. Harvey, K. F., Zhang, X. and Thomas, D. M. (2013). The Hippo pathway and human cancer. Nat. Rev. Cancer 13, 246-257.
34. Herranz, H., Hong, X. and Cohen, S. M. (2012). Mutual repression by bantam miRNA and Capicua links the EGFR/MAPK and Hippo pathways in growth control. Curr. Biol. 22, 651-657.
35. Herranz, H., Weng, R. and Cohen, S. M. (2014). Crosstalk between epithelial and mesenchymal tissues in tumorigenesis and imaginal disc development. Curr. Biol. 24, 1476-1484.
36. 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.
37. Humphrey, J. D., Dufresne, E. R. and Schwartz, M. A. (2014). Mechanotransduction and extracellular matrix homeostasis. Nat. Rev. Mol. Cell Biol. 15, 802-812.
38. Ireland, H., Kemp, R., Houghton, C., Howard, L., Clarke, A. R., Sansom, O. J. and Winton, D. J. (2004). Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-catenin. Gastroenterology 126, 1236-1246.
39. Irvine, K. D. and Harvey, K. F. (2015). Control of organ growth by patterning and Hippo signaling in Drosophila. Cold Spring Harb. Perspect. Biol. 7, a019224.
40. Jackson, E. L., Willis, N., Mercer, K., Bronson, R. T., Crowley, D., Montoya, R., Jacks, T. and Tuveson, D. A. (2001). Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev. 15, 3243-3248.
41. Jiang, H., Grenley, M. O., Bravo, M.-J., Blumhagen, R. Z. and Edgar, B. A. (2011). EGFR/Ras/MAPK signaling mediates adult midgut epithelial homeostasis and regeneration in Drosophila. Cell Stem Cell 8, 84-95.
42. Jin, Y., Xu, J., Yin, M.-X., Lu, Y., Hu, L., Li, P., Zhang, P., Yuan, Z., Ho, M. S., Ji, H. et al. (2013). Brahma is essential for Drosophila intestinal stem cell proliferation and regulated by Hippo signaling. eLife 2, e00999.
43. Jonkers, J., Meuwissen, R., van der Gulden, H., Peterse, H., van der Valk, M. and Berns, A. (2001). Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer. Nat. Genet. 29, 418-425.
44. Karim, S. A., Creedon, H., Patel, H., Carragher, N. O., Morton, J. P., Muller,W. J., Evans, T. R., Gusterson, B., Sansom, O. J. and Brunton, V. G. (2013). Dasatinib inhibits mammary tumour development in a genetically engineered mouse model. J. Pathol. 230, 430-440.
45. Kim, N.-G. and Gumbiner, B. M. (2015). Adhesion to fibronectin regulates Hippo signaling via the FAK-Src-PI3K pathway. J. Cell Biol. 210, 503-515.
46. Kohlmaier, A., Fassnacht, C., Jin, Y., Reuter, H., Begum, J., Dutta, D. and Edgar, B. A. (2015). Src kinase function controls progenitor cell pools during regeneration and tumor onset in the Drosophila intestine. Oncogene 34, 2371-2384.
47. Kono, K., Tamashiro, D. A. and Alarcon, V. B. (2014). Inhibition of RHO-ROCK signaling enhances ICM and suppresses TE characteristics through activation of Hippo signaling in the mouse blastocyst. Dev. Biol. 394, 142-155.
48. Koontz, L. M., Liu-Chittenden, Y., Yin, F., Zheng, Y., Yu, J., Huang, B., Chen, Q., Wu, S. and Pan, D. (2013). The Hippo effector Yorkie controls normal tissue growth by antagonizing scalloped-mediated default repression. Dev. Cell 25, 388-401.
49. Lawson, C. D. and Burridge, K. (2014). The on-off relationship of Rho and Rac during integrin-mediated adhesion and cell migration. Small GTPases 5, e27958.
50. Leder, A., Kuo, A., Cardiff, R. D., Sinn, E. and Leder, P. (1990). v-Ha-ras transgene abrogates the initiation step in mouse skin tumorigenesis: effects of phorbol esters and retinoic acid. Proc. Natl. Acad. Sci. USA 87, 9178-9182.
51. Lin, G., Zhang, X., Ren, J., Pang, Z., Wang, C., Xu, N. and Xi, R. (2013). Integrin signaling is required for maintenance and proliferation of intestinal stem cells in Drosophila. Dev. Biol. 377, 177-187.
52. Ling, C., Zheng, Y., Yin, F., Yu, J., Huang, J., Hong, Y., Wu, S. and Pan, D. (2010). The apical transmembrane protein Crumbs functions as a tumor suppressor that regulates Hippo signaling by binding to Expanded. Proc. Natl. Acad. Sci. USA 107, 10532-10537.
53. Liu-Chittenden, Y., Huang, B., Shim, J. S., Chen, Q., Lee, S.-J., Anders, R. A., Liu, J. O. and Pan, D. (2012). Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. Genes Dev. 26, 1300-1305.
54. Lundberg, E. and Uhlén, M. (2010). Creation of an antibody-based subcellular protein atlas. Proteomics 10, 3984-3996.
55. 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.
56. Marcotte, R., Smith, H. W., Sanguin-Gendreau, V., McDonough, R. V. and Muller, W. J. (2012). Mammary epithelial-specific disruption of c-Src impairs cell cycle progression and tumorigenesis. Proc. Natl. Acad. Sci. USA 109, 2808-2813.
57. Martin-Belmonte, F., Gassama, A., Datta, A., Yu,W., Rescher, U., Gerke, V. and Mostov, K. (2007). PTEN-mediated apical segregation of phosphoinositides controls epithelial morphogenesis through Cdc42. Cell 128, 383-397.
58. Mo, J.-S., Yu, F.-X., Gong, R., Brown, J. H. and Guan, K.-L. (2012). Regulation of the Hippo-YAP pathway by protease-activated receptors (PARs). Genes Dev. 26, 2138-2143.
59. Mohseni, M., Sun, J., Lau, A., Curtis, S., Goldsmith, J., Fox, V. L., Wei, C., Frazier, M., Samson, O.,Wong, K.-K. et al. (2014). A genetic screen identifies an LKB1-MARK signalling axis controlling the Hippo-YAP pathway. Nat. Cell Biol. 16, 108-117.
60. Morton, J. P., Karim, S. A., Graham, K., Timpson, P., Jamieson, N., Athineos, D., Doyle, B., McKay, C., Heung, M.-Y., Oien, K. A. et al. (2010). Dasatinib inhibits the development of metastases in a mouse model of pancreatic ductal adenocarcinoma. Gastroenterology 139, 292-303.
61. Nishioka, N., Inoue, K.-i., Adachi, K., Kiyonari, H., Ota, M., Ralston, A., Yabuta, N., Hirahara, S., Stephenson, R. O., Ogonuki, N. et al. (2009). The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass. Dev. Cell 16, 398-410.
62. Oh, H. and Irvine, K. D. (2008). In vivo regulation of Yorkie phosphorylation and localization. Development 135, 1081-1088.
63. Oh, H., Slattery, M., Ma, L., Crofts, A., White, K. P., Mann, R. S. and Irvine, K. D. (2013). Genome-wide association of Yorkie with chromatin and chromatinremodeling complexes. Cell Rep. 3, 309-318.
64. Pan, D. (2010). The Hippo signaling pathway in development and cancer. Dev. Cell 19, 491-505.
65. Pan, D. (2015). YAPing Hippo forecasts a new target for lung cancer prevention and treatment. J. Clin. Oncol. 33, 2311-2313.
66. Park, H. W., Kim, Y. C., Yu, B., Moroishi, T., Mo, J.-S., Plouffe, S. W., Meng, Z., Lin, K. C., Yu, F.-X., Alexander, C. M. et al. (2015). Alternative Wnt signaling activates YAP/TAZ. Cell 162, 780-794.
67. Piccolo, S., Cordenonsi, M. and Dupont, S. (2013). Molecular pathways: YAP and TAZ take center stage in organ growth and tumorigenesis. Clin. Cancer Res. 19, 4925-4930.
68. Piwko-Czuchra, A., Koegel, H., Meyer, H., Bauer, M., Werner, S., Brakebusch, C. and Fässler, R. (2009). Beta1 integrin-mediated adhesion signalling is essential for epidermal progenitor cell expansion. PLoS ONE 4, e5488.
69. Pontén, F., Jirström, K. and Uhlen, M. (2008). The Human Protein Atlas-a tool for pathology. J. Pathol. 216, 387-393.
70. Raghavan, S., Bauer, C., Mundschau, G., Li, Q. and Fuchs, E. (2000). Conditional ablation of beta1 integrin in skin. Severe defects in epidermal proliferation, basement membrane formation, and hair follicle invagination. J. Cell Biol. 150, 1149-1160.
71. Rauskolb, C., Pan, G., Reddy, B. V. V. G., Oh, H. and Irvine, K. D. (2011). Zyxin links fat signaling to the Hippo pathway. PLoS Biol. 9, e1000624.
72. Rauskolb, C., Sun, S., Sun, G., Pan, Y. and Irvine, K. D. (2014). Cytoskeletal tension inhibits Hippo signaling through an Ajuba-Warts complex. Cell 158, 143-156.
73. Reginensi, A., Hoshi, M., Boualia, S. K., Bouchard, M., Jain, S. and McNeill, H. (2015). Yap and Taz are required for Ret-dependent urinary tract morphogenesis. Development 142, 2696-2703.
74. Ridgway, R. A., Serrels, B., Mason, S., Kinnaird, A., Muir, M., Patel, H., Muller, W. J., Sansom, O. J. and Brunton, V. G. (2012). Focal adhesion kinase is required for beta-catenin-induced mobilization of epidermal stem cells. Carcinogenesis 33, 2369-2376.
75. Sansores-Garcia, L., Bossuyt,W.,Wada, K.-I., Yonemura, S., Tao, C., Sasaki, H. and Halder, G. (2011). Modulating F-actin organization induces organ growth by affecting the Hippo pathway. EMBO J. 30, 2325-2335.
76. Sansores-Garcia, L., Atkins, M., Moya, I. M., Shahmoradgoli, M., Tao, C., Mills, G. B. and Halder, G. (2013). Mask is required for the activity of the Hippo pathway effector Yki/YAP. Curr. Biol. 23, 229-235.
77. Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J. et al. (2009). Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459, 262-265.
78. Schlegelmilch, K., Mohseni, M., Kirak, O., Pruszak, J., Rodriguez, J. R., Zhou, D., Kreger, B. T., Vasioukhin, V., Avruch, J., Brummelkamp, T. R. et al. (2011). Yap1 acts downstream of alpha-catenin to control epidermal proliferation. Cell 144, 782-795.
79. Serrels, B., Serrels, A., Mason, S. M., Baldeschi, C., Ashton, G. H., Canel, M., Mackintosh, L. J., Doyle, B., Green, T. P., Frame, M. C. et al. (2009). A novel Src kinase inhibitor reduces tumour formation in a skin carcinogenesis model. Carcinogenesis 30, 249-257.
80. 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.
81. Shibata, H., Toyama, K., Shioya, H., Ito, M., Hirota, M., Hasegawa, S., Matsumoto, H., Takano, H., Akiyama, T., Toyoshima, K. et al. (1997). Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene. Science 278, 120-123.
82. Sidor, C. M., Brain, R. and Thompson, B. J. (2013). Mask proteins are cofactors of Yorkie/YAP in the Hippo pathway. Curr. Biol. 23, 223-228.
83. Singh, P., Chen, C., Pal-Ghosh, S., Stepp, M. A., Sheppard, D. and Van De Water, L. (2009). Loss of integrin alpha9beta1 results in defects in proliferation, causing poor re-epithelialization during cutaneous wound healing. J. Invest. Dermatol. 129, 217-228.
84. Sorrentino, G., Ruggeri, N., Specchia, V., Cordenonsi, M., Mano, M., Dupont, S., Manfrin, A., Ingallina, E., Sommaggio, R., Piazza, S. et al. (2014). Metabolic control of YAP and TAZ by the mevalonate pathway. Nat. Cell Biol. 16, 357-366.
85. Staley, B. K. and Irvine, K. D. (2010). Warts and Yorkie mediate intestinal regeneration by influencing stem cell proliferation. Curr. Biol. 20, 1580-1587.
86. Strassburger, K., Tiebe, M., Pinna, F., Breuhahn, K. and Teleman, A. A. (2012). Insulin/IGF signaling drives cell proliferation in part via Yorkie/YAP. Dev. Biol. 367, 187-196.
87. Sun, S., Reddy, B. V. V. G. and Irvine, K. D. (2015). Localization of Hippo signalling complexes and Warts activation in vivo. Nat. Commun. 6, 8402.
88. Szymaniak, A. D., Mahoney, J. E., Cardoso, W. V. and Varelas, X. (2015). Crumbs3-mediated polarity directs airway epithelial cell fate through the Hippo pathway effector yap. Dev. Cell 34, 283-296.
89. Taniguchi, K., Wu, L.-W., Grivennikov, S. I., de Jong, P. R., Lian, I., Yu, F.-X., Wang, K., Ho, S. B., Boland, B. S., Chang, J. T. et al. (2015). A gp130-Src-YAP module links inflammation to epithelial regeneration. Nature 519, 57-62.
90. Thompson, B. J. (2013). Cell polarity: models and mechanisms from yeast, worms and flies. Development 140, 13-21.
91. Uhlen, M., Björling, E., Agaton, C., Szigyarto, C. A.-K., Amini, B., Andersen, E., Andersson, A.-C., Angelidou, P., Asplund, A., Asplund, C. et al. (2005). A human protein atlas for normal and cancer tissues based on antibody proteomics. Mol. Cell. Proteomics 4, 1920-1932.
92. Uhlen, M., Oksvold, P., Fagerberg, L., Lundberg, E., Jonasson, K., Forsberg, M., Zwahlen, M., Kampf, C., Wester, K., Hober, S. et al. (2010). Towards a knowledge-based Human Protein Atlas. Nat. Biotechnol. 28, 1248-1250.
93. Uhlen, M., Fagerberg, L., Hallstrom, B. M., Lindskog, C., Oksvold, P., Mardinoglu, A., Sivertsson, A., Kampf, C., Sjostedt, E., Asplund, A. et al. (2015). Proteomics. Tissue-based map of the human proteome. Science 347, 1260419.
94. Valeri, N., Braconi, C., Gasparini, P., Murgia, C., Lampis, A., Paulus-Hock, V., Hart, J. R., Ueno, L., Grivennikov, S. I., Lovat, F. et al. (2014). MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer. Cancer Cell 25, 469-483.
95. 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-beta-SMAD pathway. Dev. Cell 19, 831-844.
96. Vassilev, A., Kaneko, K. J., Shu, H., Zhao, Y. and DePamphilis, M. L. (2001). TEAD/TEF transcription factors utilize the activation domain of YAP65, a Src/ Yes-associated protein localized in the cytoplasm. Genes Dev. 15, 1229-1241.
97. Willecke, M., Toggweiler, J. and Basler, K. (2011). Loss of PI3K blocks cell-cycle progression in a Drosophila tumor model. Oncogene 30, 4067-4074.
98. 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.
99. Xu, N., Wang, S. Q., Tan, D., Gao, Y., Lin, G. and Xi, R. (2011). EGFR, Wingless and JAK/STAT signaling cooperatively maintain Drosophila intestinal stem cells. Dev. Biol. 354, 31-43.
100. Yin, F., Yu, J., Zheng, Y., Chen, Q., Zhang, N. and Pan, D. (2013). Spatial organization of Hippo signaling at the plasma membrane mediated by the tumor suppressor Merlin/NF2. Cell 154, 1342-1355.
101. Yu, J., Zheng, Y., Dong, J., Klusza, S., Deng, W.-M. and Pan, D. (2010). Kibra functions as a tumor suppressor protein that regulates Hippo signaling in conjunction with Merlin and Expanded. Dev. Cell 18, 288-299.
102. Yu, F.-X., Zhao, B., Panupinthu, N., Jewell, J. L., Lian, I., Wang, L. H., Zhao, J., Yuan, H., Tumaneng, K., Li, H. et al. (2012). Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell 150, 780-791.
103. Yu, F.-X., Zhang, Y., Park, H.W., Jewell, J. L., Chen, Q., Deng, Y., Pan, D., Taylor, S. S., Lai, Z.-C. and Guan, K.-L. (2013). Protein kinase A activates the Hippo pathway to modulate cell proliferation and differentiation. Genes Dev. 27, 1223-1232.
104. Zanconato, F., Forcato, M., Battilana, G., Azzolin, L., Quaranta, E., Bodega, B., Rosato, A., Bicciato, S., Cordenonsi, M. and Piccolo, S. (2015). Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. Nat. Cell Biol. 17, 1218-1227.
105. 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 homeostasis in mammals. Dev. Cell 19, 27-38.
106. Zhang, H., Pasolli, H. A. and Fuchs, E. (2011a). Yes-associated protein (YAP) transcriptional coactivator functions in balancing growth and differentiation in skin. Proc. Natl. Acad. Sci. USA 108, 2270-2275.
107. Zhang, X., Milton, C. C., Poon, C. L. C., Hong,W. and Harvey, K. F. (2011b). Wbp2 cooperates with Yorkie to drive tissue growth downstream of the Salvador-Warts-Hippo pathway. Cell Death Differ. 18, 1346-1355.
108. Zhao, B.,Wei, X., Li,W., Udan, R. S., Yang, Q., Kim, J., Xie, J., Ikenoue, T., Yu, J., Li, L. et al. (2007). Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev. 21, 2747-2761.
109. Zhao, R., Fallon, T. R., Saladi, S. V., Pardo-Saganta, A., Villoria, J., Mou, H., Vinarsky, V., Gonzalez-Celeiro, M., Nunna, N., Hariri, L. P. et al. (2014). Yap tunes airway epithelial size and architecture by regulating the identity, maintenance, and self-renewal of stem cells. Dev. Cell 30, 151-165.