WNT and β-Catenin in Cancer: Genes and Therapy

Literature Cited

1. Amit S, Hatzubai A, Birman Y, Andersen JS, Ben-Shushan E et al. 2002. Axin-mediated CKI phosphorylation of β-catenin at Ser 45: a molecular switch for the Wnt pathway. Genes Dev 16:1066–76
   [Google Scholar]
2. Avgustinova A, Iravani M, Robertson D, Fearns A, Gao Q et al. 2016. Tumour cell-derived Wnt7a recruits and activates fibroblasts to promote tumour aggressiveness. Nat. Commun. 7:10305
   [Google Scholar]
3. Barker N, Huch M, Kujala P, van de Wetering M, Snippert HJ et al. 2010. Lgr5^+ve stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 6:25–36
   [Google Scholar]
4. Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H et al. 2009. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457:608–11
   [Google Scholar]
5. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M et al. 2007. Identification of stem cells in small intestine and colon by marker gene Lgr5. . Nature 449:1003–7
   [Google Scholar]
6. Becht E, de Reynies A, Giraldo NA, Pilati C, Buttard B et al. 2016. Immune and stromal classification of colorectal cancer is associated with molecular subtypes and relevant for precision immunotherapy. Clin. Cancer Res. 22:4057–66
   [Google Scholar]
7. Behrens J, Jerchow BA, Wurtele M, Grimm J, Asbrand C et al. 1998. Functional interaction of an axin homolog, conductin, with β-catenin, APC, and GSK3β. Science 280:596–99
   [Google Scholar]
8. Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D et al. 1996. Functional interaction of β-catenin with the transcription factor LEF-1. Nature 382:638–42
   [Google Scholar]
9. Binnewies M, Roberts EW, Kersten K, Chan V, Fearon DF et al. 2018. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat. Med. 24:541–50
   [Google Scholar]
10. Bond CE, McKeone DM, Kalimutho M, Bettington ML, Pearson SA et al. 2016. RNF43 and ZNRF3 are commonly altered in serrated pathway colorectal tumorigenesis. Oncotarget 7:70589–600
    [Google Scholar]
11. Buchert M, Athineos D, Abud HE, Burke ZD, Faux MC et al. 2010. Genetic dissection of differential signaling threshold requirements for the Wnt/β-catenin pathway in vivo. PLOS Genet 6:e1000816
    [Google Scholar]
12. Cadoret A, Ovejero C, Saadi-Kheddouci S, Souil E, Fabre M et al. 2001. Hepatomegaly in transgenic mice expressing an oncogenic form of β-catenin. Cancer Res 61:3245–49
    [Google Scholar]
13. Cairo S, Armengol C, De Reynies A, Wei Y, Thomas E et al. 2008. Hepatic stem-like phenotype and interplay of Wnt/β-catenin and Myc signaling in aggressive childhood liver cancer. Cancer Cell 14:471–84
    [Google Scholar]
14. Cancer Genome Atlas Res. Netw 2017. Integrated genomic characterization of pancreatic ductal adenocarcinoma. Cancer Cell 32:185–203.e13
    [Google Scholar]
15. Cancer Genome Atlas Res. Netw. Kandoth C, Schultz N, Cherniack AD, Akbani R et al. 2013. Integrated genomic characterization of endometrial carcinoma. Nature 497:67–73
    [Google Scholar]
16. Cancer Genome Atlas Res. Netw. Muzny DM, Bainbridge MN, Chang K, Dinh HH et al. 2012. Comprehensive molecular characterization of human colon and rectal cancer. Nature 487:330–37
    [Google Scholar]
17. Carmon KS, Loose DS. 2008. Secreted frizzled-related protein 4 regulates two Wnt7a signaling pathways and inhibits proliferation in endometrial cancer cells. Mol. Cancer Res. 6:1017–28
    [Google Scholar]
18. Casey SC, Tong L, Li Y, Do R, Walz S et al. 2016. MYC regulates the antitumor immune response through CD47 and PD-L1. Science 352:227–31
    [Google Scholar]
19. Colnot S, Decaens T, Niwa-Kawakita M, Godard C, Hamard G et al. 2004. Liver-targeted disruption of Apc in mice activates β-catenin signaling and leads to hepatocellular carcinomas. PNAS 101:17216–21
    [Google Scholar]
20. de Lau W, Barker N, Low TY, Koo BK, Li VS et al. 2011. Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature 476:293–97
    [Google Scholar]
21. de Lau W, Peng WC, Gros P, Clevers H 2014. The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength. Genes Dev 28:305–16
    [Google Scholar]
22. de Sousa e Melo F, Colak S, Buikhuisen J, Koster J, Cameron K et al. 2011. Methylation of cancer-stem-cell-associated Wnt target genes predicts poor prognosis in colorectal cancer patients. Cell Stem Cell 9:476–85
    [Google Scholar]
23. de Sousa e Melo F, Kurtova AV, Harnoss JM, Kljavin N, Hoeck JD et al. 2017. A distinct role for Lgr5⁺ stem cells in primary and metastatic colon cancer. Nature 543:676–80
    [Google Scholar]
24. Delmas V, Beermann F, Martinozzi S, Carreira S, Ackermann J et al. 2007. β-catenin induces immortalization of melanocytes by suppressing p16^INK4a expression and cooperates with N-Ras in melanoma development. Genes Dev 21:2923–35
    [Google Scholar]
25. Dow LE, O'Rourke KP, Simon J, Tschaharganeh DF, van Es JH et al. 2015. Apc restoration promotes cellular differentiation and reestablishes crypt homeostasis in colorectal cancer. Cell 161:1539–52
    [Google Scholar]
26. Emami KH, Nguyen C, Ma H, Kim DH, Jeong KW et al. 2004. A small molecule inhibitor of β-catenin/CREB-binding protein transcription. PNAS 101:12682–87 Erratum. 2004 PNAS 101:16707
    [Google Scholar]
27. Farin HF, Jordens I, Mosa MH, Basak O, Korving J et al. 2016. Visualization of a short-range Wnt gradient in the intestinal stem-cell niche. Nature 530:340–43
    [Google Scholar]
28. Feng GJ, Cotta W, Wei XQ, Poetz O, Evans R et al. 2012. Conditional disruption of Axin1 leads to development of liver tumors in mice. Gastroenterology 143:1650–59
    [Google Scholar]
29. Fessler E, Medema JP. 2016. Colorectal cancer subtypes: developmental origin and microenvironmental regulation. Trends Cancer 2:505–18
    [Google Scholar]
30. Flanagan DJ, Barker N, Costanzo NSD, Mason EA, Gurney A et al. 2019. Frizzled-7 is required for Wnt signaling in gastric tumors with and without Apc mutations. Cancer Res 79:970–81
    [Google Scholar]
31. Gay DM, Ridgway RA, Mueller M, Hodder MC, Hedley A et al. 2019. Loss of BCL9/9l suppresses Wnt driven tumourigenesis in models that recapitulate human cancer. Nat. Commun. 10:723
    [Google Scholar]
32. Glinka A, Wu W, Delius H, Monaghan AP, Blumenstock C, Niehrs C 1998. Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature 391:357–62
    [Google Scholar]
33. Gnad T, Feoktistova M, Leverkus M, Lendeckel U, Naumann M 2010. Helicobacter pylori-induced activation of β-catenin involves low density lipoprotein receptor-related protein 6 and Dishevelled. Mol. Cancer 9:31
    [Google Scholar]
34. Gong X, Azhdarinia A, Ghosh SC, Xiong W, An Z et al. 2016. LGR5-targeted antibody–drug conjugate eradicates gastrointestinal tumors and prevents recurrence. Mol. Cancer Ther. 15:1580–90
    [Google Scholar]
35. Grasso CS, Giannakis M, Wells DK, Hamada T, Mu XJ et al. 2018. Genetic mechanisms of immune evasion in colorectal cancer. Cancer Discov 8:730–49
    [Google Scholar]
36. Groden J, Thliveris A, Samowitz W, Carlson M, Gelbert L et al. 1991. Identification and characterization of the familial adenomatous polyposis coli gene. Cell 66:589–600
    [Google Scholar]
37. Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A et al. 2015. The consensus molecular subtypes of colorectal cancer. Nat. Med. 21:1350–56
    [Google Scholar]
38. Han T, Schatoff EM, Murphy C, Zafra MP, Wilkinson JE et al. 2017. R-Spondin chromosome rearrangements drive Wnt-dependent tumour initiation and maintenance in the intestine. Nat. Commun. 8:15945
    [Google Scholar]
39. Hao HX, Xie Y, Zhang Y, Charlat O, Oster E et al. 2012. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature 485:195–200
    [Google Scholar]
40. Harada N, Miyoshi H, Murai N, Oshima H, Tamai Y et al. 2002. Lack of tumorigenesis in the mouse liver after adenovirus-mediated expression of a dominant stable mutant of β-catenin. Cancer Res 62:1971–77
    [Google Scholar]
41. He TC, Sparks AB, Rago C, Hermeking H, Zawel L et al. 1998. Identification of c-MYC as a target of the APC pathway. Science 281:1509–12
    [Google Scholar]
42. Hodis E, Watson IR, Kryukov GV, Arold ST, Imielinski M et al. 2012. A landscape of driver mutations in melanoma. Cell 150:251–63
    [Google Scholar]
43. Hoffmans R, Stadeli R, Basler K 2005. Pygopus and legless provide essential transcriptional coactivator functions to Armadillo/β-catenin. Curr. Biol. 15:1207–11
    [Google Scholar]
44. Horst D, Chen J, Morikawa T, Ogino S, Kirchner T, Shivdasani RA 2012. Differential WNT activity in colorectal cancer confers limited tumorigenic potential and is regulated by MAPK signaling. Cancer Res 72:1547–56
    [Google Scholar]
45. Hou X, Tan Y, Li M, Dey SK, Das SK 2004. Canonical Wnt signaling is critical to estrogen-mediated uterine growth. Mol. Endocrinol. 18:3035–49
    [Google Scholar]
46. Huang SM, Mishina YM, Liu S, Cheung A, Stegmeier F et al. 2009. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 461:614–20
    [Google Scholar]
47. Huch M, Dorrell C, Boj SF, van Es JH, Li VS et al. 2013. In vitro expansion of single Lgr5⁺ liver stem cells induced by Wnt-driven regeneration. Nature 494:247–50
    [Google Scholar]
48. Huels DJ, Bruens L, Hodder MC, Cammareri P, Campbell AD et al. 2018. Wnt ligands influence tumour initiation by controlling the number of intestinal stem cells. Nat. Commun. 9:1132
    [Google Scholar]
49. Huels DJ, Ridgway RA, Radulescu S, Leushacke M, Campbell AD et al. 2015. E-cadherin can limit the transforming properties of activating β-catenin mutations. EMBO J 34:2321–33
    [Google Scholar]
50. Iglesia MD, Parker JS, Hoadley KA, Serody JS, Perou CM, Vincent BG 2016. Genomic analysis of immune cell infiltrates across 11 tumor types. J. Natl. Cancer Inst. 108:djw144
    [Google Scholar]
51. Ikeda S, Kishida S, Yamamoto H, Murai H, Koyama S, Kikuchi A 1998. Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3β and β-catenin and promotes GSK-3β-dependent phosphorylation of β-catenin. EMBO J 17:1371–84
    [Google Scholar]
52. Ikeya M, Lee SM, Johnson JE, McMahon AP, Takada S 1997. Wnt signalling required for expansion of neural crest and CNS progenitors. Nature 389:966–70
    [Google Scholar]
53. Isaacsson Velho P, Fu W, Wang H, Mirkheshti N, Qazi F et al. 2020. Wnt-pathway activating mutations are associated with resistance to first-line abiraterone and enzalutamide in castration-resistant prostate cancer. Eur. Urol. 77:114–21
    [Google Scholar]
54. Jaks V, Barker N, Kasper M, van Es JH, Snippert HJ et al. 2008. Lgr5 marks cycling, yet long-lived, hair follicle stem cells. Nat. Genet. 40:1291–99
    [Google Scholar]
55. Janda CY, Waghray D, Levin AM, Thomas C, Garcia KC 2012. Structural basis of Wnt recognition by Frizzled. Science 337:59–64
    [Google Scholar]
56. Jeong JW, Lee HS, Franco HL, Broaddus RR, Taketo MM et al. 2009. β-catenin mediates glandular formation and dysregulation of β-catenin induces hyperplasia formation in the murine uterus. Oncogene 28:31–40
    [Google Scholar]
57. Jiang X, Hao HX, Growney JD, Woolfenden S, Bottiglio C et al. 2013. Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma. PNAS 110:12649–54
    [Google Scholar]
58. Johansson J, Naszai M, Hodder MC, Pickering KA, Miller BW et al. 2019. RAL GTPases drive intestinal stem cell function and regeneration through internalization of Wnt signalosomes. Cell Stem Cell 24:592–607
    [Google Scholar]
59. Junttila MR, Mao W, Wang X, Wang BE, Pham T et al. 2015. Targeting LGR5⁺ cells with an antibody-drug conjugate for the treatment of colon cancer. Sci. Transl. Med. 7:314ra186
    [Google Scholar]
60. Kakugawa S, Langton PF, Zebisch M, Howell S, Chang TH et al. 2015. Notum deacylates Wnt proteins to suppress signalling activity. Nature 519:187–92
    [Google Scholar]
61. Kazanskaya O, Glinka A, del Barco Barrantes I, Stannek P, Niehrs C, Wu W 2004. R-Spondin2 is a secreted activator of Wnt/β-catenin signaling and is required for Xenopus myogenesis. Dev. Cell 7:525–34
    [Google Scholar]
62. Kim B, Byun SJ, Kim YA, Kim JE, Lee BL et al. 2010. Cell cycle regulators, APC/β-catenin, NF-κB and Epstein-Barr virus in gastric carcinomas. Pathology 42:58–65
    [Google Scholar]
63. Kinzler KW, Nilbert MC, Su LK, Vogelstein B, Bryan TM et al. 1991. Identification of FAP locus genes from chromosome 5q21. Science 253:661–65
    [Google Scholar]
64. Koo BK, Spit M, Jordens I, Low TY, Stange DE et al. 2012. Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature 488:665–69
    [Google Scholar]
65. Koo BK, van Es JH, van den Born M, Clevers H 2015. Porcupine inhibitor suppresses paracrine Wnt-driven growth of Rnf43;Znrf3-mutant neoplasia. PNAS 112:7548–50
    [Google Scholar]
66. Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R et al. 1997. Constitutive transcriptional activation by a β-catenin-Tcf complex in APC^−/− colon carcinoma. Science 275:1784–87
    [Google Scholar]
67. Kortlever RM, Sodir NM, Wilson CH, Burkhart DL, Pellegrinet L et al. 2017. Myc cooperates with Ras by programming inflammation and immune suppression. Cell 171:1301–15.e14
    [Google Scholar]
68. Kurayoshi M, Oue N, Yamamoto H, Kishida M, Inoue A et al. 2006. Expression of Wnt-5a is correlated with aggressiveness of gastric cancer by stimulating cell migration and invasion. Cancer Res 66:10439–48
    [Google Scholar]
69. Larue L, Delmas V. 2006. The WNT/β-catenin pathway in melanoma. Front. Biosci. 11:733–42
    [Google Scholar]
70. Lenos KJ, Miedema DM, Lodestijn SC, Nijman LE, van den Bosch T et al. 2018. Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer. Nat. Cell Biol. 20:1193–202
    [Google Scholar]
71. Leung C, Tan SH, Barker N 2018. Recent advances in Lgr5⁺ stem cell research. Trends Cell Biol 28:380–91
    [Google Scholar]
72. Li B, Flaveny CA, Giambelli C, Fei DL, Han L et al. 2014. Repurposing the FDA-approved pinworm drug pyrvinium as a novel chemotherapeutic agent for intestinal polyposis. PLOS ONE 9:e101969
    [Google Scholar]
73. Li VS, Ng SS, Boersema PJ, Low TY, Karthaus WR et al. 2012. Wnt signaling through inhibition of β-catenin degradation in an intact Axin1 complex. Cell 149:1245–56
    [Google Scholar]
74. Lim X, Tan SH, Koh WL, Chau RM, Yan KS et al. 2013. Interfollicular epidermal stem cells self-renew via autocrine Wnt signaling. Science 342:1226–30
    [Google Scholar]
75. Linnekamp JF, Hooff SRV, Prasetyanti PR, Kandimalla R, Buikhuisen JY et al. 2018. Consensus molecular subtypes of colorectal cancer are recapitulated in in vitro and in vivo models. Cell Death Differ 25:616–33
    [Google Scholar]
76. Liu C, Li Y, Semenov M, Han C, Baeg GH et al. 2002. Control of β-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108:837–47
    [Google Scholar]
77. Liu Y, Meng F, Xu Y, Yang S, Xiao M et al. 2013. Overexpression of Wnt7a is associated with tumor progression and unfavorable prognosis in endometrial cancer. Int. J. Gynecol. Cancer 23:304–11
    [Google Scholar]
78. Liu Y, Patel L, Mills GB, Lu KH, Sood AK et al. 2014. Clinical significance of CTNNB1 mutation and Wnt pathway activation in endometrioid endometrial carcinoma. J. Natl. Cancer Inst. 106:dju245
    [Google Scholar]
79. Logan CY, Nusse R. 2004. The Wnt signaling pathway in development and disease. Annu. Rev. Cell Dev. Biol. 20:781–810
    [Google Scholar]
80. Longerich T, Endris V, Neumann O, Rempel E, Kirchner M et al. 2019. RSPO2 gene rearrangement: a powerful driver of β-catenin activation in liver tumours. Gut 68:1140–42
    [Google Scholar]
81. Luke JJ, Bao R, Sweis RF, Spranger S, Gajewski TF 2019. WNT/β-catenin pathway activation correlates with immune exclusion across human cancers. Clin. Cancer Res. 25:3074–83
    [Google Scholar]
82. Madan B, McDonald MJ, Foxa GE, Diegel CR, Williams BO, Virshup DM 2018. Bone loss from Wnt inhibition mitigated by concurrent alendronate therapy. Bone Res 6:17
    [Google Scholar]
83. Malanchi I, Santamaria-Martinez A, Susanto E, Peng H, Lehr HA et al. 2011. Interactions between cancer stem cells and their niche govern metastatic colonization. Nature 481:85–89
    [Google Scholar]
84. Mao J, Fan S, Ma W, Fan P, Wang B et al. 2014. Roles of Wnt/β-catenin signaling in the gastric cancer stem cells proliferation and salinomycin treatment. Cell Death Dis 5:e1039
    [Google Scholar]
85. Menon M, Elliott R, Bowers L, Balan N, Rafiq R et al. 2019. A novel tankyrase inhibitor, MSC2504877, enhances the effects of clinical CDK4/6 inhibitors. Sci. Rep. 9:201
    [Google Scholar]
86. Michels BE, Mosa MH, Grebbin BM, Yepes D, Darvishi T et al. 2019. Human colon organoids reveal distinct physiologic and oncogenic Wnt responses. J. Exp. Med. 216:704–20
    [Google Scholar]
87. Mieszczanek J, van Tienen LM, Ibrahim AEK, Winton DJ, Bienz M 2019. Bcl9 and Pygo synergise downstream of Apc to effect intestinal neoplasia in FAP mouse models. Nat. Commun. 10:724
    [Google Scholar]
88. Minde DP, Anvarian Z, Rudiger SG, Maurice MM 2011. Messing up disorder: How do missense mutations in the tumor suppressor protein APC lead to cancer. ? Mol. Cancer 10:101
    [Google Scholar]
89. Molenaar M, van de Wetering M, Oosterwegel M, Peterson-Maduro J, Godsave S et al. 1996. XTcf-3 transcription factor mediates β-catenin-induced axis formation in Xenopus embryos. Cell 86:391–99
    [Google Scholar]
90. Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H et al. 1997. Activation of β-catenin-Tcf signaling in colon cancer by mutations in β-catenin or APC. Science 275:1787–90
    [Google Scholar]
91. Mulligan KA, Fuerer C, Ching W, Fish M, Willert K, Nusse R 2012. Secreted Wingless-interacting molecule (Swim) promotes long-range signaling by maintaining Wingless solubility. PNAS 109:370–77
    [Google Scholar]
92. Murata-Kamiya N, Kurashima Y, Teishikata Y, Yamahashi Y, Saito Y et al. 2007. Helicobacter pylori CagA interacts with E-cadherin and deregulates the β-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells. Oncogene 26:4617–26
    [Google Scholar]
93. Ng A, Tan S, Singh G, Rizk P, Swathi Y et al. 2014. Lgr5 marks stem/progenitor cells in ovary and tubal epithelia. Nat. Cell Biol. 16:745–57
    [Google Scholar]
94. Niehrs C. 2012. The complex world of WNT receptor signalling. Nat. Rev. Mol. Cell Biol. 13:767–79
    [Google Scholar]
95. Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H et al. 1991. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 253:665–69
    [Google Scholar]
96. Nusse R, Clevers H. 2017. Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell 169:985–99
    [Google Scholar]
97. Nusse R, Varmus HE. 1982. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 31:99–109
    [Google Scholar]
98. Nusslein-Volhard C, Wieschaus E. 1980. Mutations affecting segment number and polarity in Drosophila. . Nature 287:795–801
    [Google Scholar]
99. Oshima H, Matsunaga A, Fujimura T, Tsukamoto T, Taketo MM, Oshima M 2006. Carcinogenesis in mouse stomach by simultaneous activation of the Wnt signaling and prostaglandin E2 pathway. Gastroenterology 131:1086–95
    [Google Scholar]
100. Palles C, Cazier JB, Howarth KM, Domingo E, Jones AM et al. 2013. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat. Genet. 45:136–44
     [Google Scholar]
101. Powell AE, Vlacich G, Zhao ZY, McKinley ET, Washington MK et al. 2014. Inducible loss of one Apc allele in Lrig1-expressing progenitor cells results in multiple distal colonic tumors with features of familial adenomatous polyposis. Am. J. Physiol. Gastrointest. Liver Physiol. 307:G16–23
     [Google Scholar]
102. Radulescu S, Ridgway RA, Cordero J, Athineos D, Salgueiro P et al. 2013. Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation. Oncogene 32:2048–57
     [Google Scholar]
103. Reed KR, Athineos D, Meniel VS, Wilkins JA, Ridgway RA et al. 2008. β-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of APC loss in the liver. PNAS 105:18919–23
     [Google Scholar]
104. Riese J, Yu X, Munnerlyn A, Eresh S, Hsu SC et al. 1997. LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic. Cell 88:777–87
     [Google Scholar]
105. Risinger JI, Maxwell GL, Chandramouli GV, Aprelikova O, Litzi T et al. 2005. Gene expression profiling of microsatellite unstable and microsatellite stable endometrial cancers indicates distinct pathways of aberrant signaling. Cancer Res 65:5031–37
     [Google Scholar]
106. Robinson D, Van Allen EM, Wu YM, Schultz N, Lonigro RJ et al. 2015. Integrative clinical genomics of advanced prostate cancer. Cell 161:51215–28
     [Google Scholar]
107. Rubinfeld B, Souza B, Albert I, Muller O, Chamberlain SH et al. 1993. Association of the APC gene product with β-catenin. Science 262:1731–34
     [Google Scholar]
108. Salahshor S, Woodgett JR. 2005. The links between axin and carcinogenesis. J Clin. Pathol. 58:225–36
     [Google Scholar]
109. Sano M, Driscoll DR, DeJesus-Monge WE, Quattrochi B, Appleman VA et al. 2016. Activation of WNT/β-catenin signaling enhances pancreatic cancer development and the malignant potential via up-regulation of Cyr61. Neoplasia 18:785–94
     [Google Scholar]
110. Sansom OJ. 2009. Tissue-specific tumour suppression by APC. Adv. Exp. Med. Biol. 656:107–18
     [Google Scholar]
111. Sansom OJ, Meniel VS, Muncan V, Phesse TJ, Wilkins JA et al. 2007. Myc deletion rescues Apc deficiency in the small intestine. Nature 446:676–79
     [Google Scholar]
112. Sansom OJ, Reed KR, Hayes AJ, Ireland H, Brinkmann H et al. 2004. Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration. Genes Dev 18:1385–90
     [Google Scholar]
113. Sarkar A, Huebner AJ, Sulahian R, Anselmo A, Xu X et al. 2016. Sox2 suppresses gastric tumorigenesis in mice. Cell Rep 16:1929–41
     [Google Scholar]
114. Sato N, Meijer L, Skaltsounis L, Greengard P, Brivanlou AH 2004. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat. Med. 10:55–63
     [Google Scholar]
115. Satoh S, Daigo Y, Furukawa Y, Kato T, Miwa N et al. 2000. AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1. . Nat. Genet 24:245–50
     [Google Scholar]
116. Seino T, Kawasaki S, Shimokawa M, Tamagawa H, Toshimitsu K et al. 2018. Human pancreatic tumor organoids reveal loss of stem cell niche factor dependence during disease progression. Cell Stem Cell 22:454–67.e6
     [Google Scholar]
117. Seshagiri S, Stawiski EW, Durinck S, Modrusan Z, Storm EE et al. 2012. Recurrent R-spondin fusions in colon cancer. Nature 488:660–64
     [Google Scholar]
118. Shimokawa M, Ohta Y, Nishikori S, Matano M, Takano A et al. 2017. Visualization and targeting of LGR5⁺ human colon cancer stem cells. Nature 545:187–92
     [Google Scholar]
119. Sigal M, Rothenberg ME, Logan CY, Lee JY, Honaker RW et al. 2015. Helicobacterpylori activates and expands Lgr5⁺ stem cells through direct colonization of the gastric glands. Gastroenterology 148:1392–404.e21
     [Google Scholar]
120. Sinner D, Kordich JJ, Spence JR, Opoka R, Rankin S et al. 2007. Sox17 and Sox4 differentially regulate β-catenin/T-cell factor activity and proliferation of colon carcinoma cells. Mol. Cell. Biol. 27:7802–15
     [Google Scholar]
121. Spranger S, Bao R, Gajewski TF 2015. Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature 523:231–35
     [Google Scholar]
122. Stadeli R, Hoffmans R, Basler K 2006. Transcription under the control of nuclear Arm/β-catenin. Curr. Biol. 16:R378–85
     [Google Scholar]
123. Steinhart Z, Pavlovic Z, Chandrashekhar M, Hart T, Wang X et al. 2017. Genome-wide CRISPR screens reveal a Wnt–FZD5 signaling circuit as a druggable vulnerability of RNF43-mutant pancreatic tumors. Nat. Med. 23:60–68
     [Google Scholar]
124. Storm EE, Durinck S, de Sousa e Melo F, Tremayne J, Kljavin N et al. 2016. Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function. Nature 529:97–100
     [Google Scholar]
125. Su LK, Vogelstein B, Kinzler KW 1993. Association of the APC tumor suppressor protein with catenins. Science 262:1734–37
     [Google Scholar]
126. Suzuki M, Mimuro H, Kiga K, Fukumatsu M, Ishijima N et al. 2009. Helicobacter pylori CagA phosphorylation-independent function in epithelial proliferation and inflammation. Cell Host Microbe 5:23–34
     [Google Scholar]
127. Sveen A, Bruun J, Eide PW, Eilertsen IA, Ramirez L et al. 2018. Colorectal cancer consensus molecular subtypes translated to preclinical models uncover potentially targetable cancer cell dependencies. Clin. Cancer Res. 24:794–806
     [Google Scholar]
128. Tahara E. 1995. Molecular biology of gastric cancer. World J. Surg. 19:484–8
     [Google Scholar]
129. Takada K, Zhu D, Bird GH, Sukhdeo K, Zhao JJ et al. 2012. Targeted disruption of the BCL9/β-catenin complex inhibits oncogenic Wnt signaling. Sci. Transl. Med. 4:148ra17
     [Google Scholar]
130. Tammela T, Sanchez-Rivera FJ, Cetinbas NM, Wu K, Joshi NS et al. 2017. A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma. Nature 545:355–59
     [Google Scholar]
131. Tan X, Apte U, Micsenyi A, Kotsagrelos E, Luo JH et al. 2005. Epidermal growth factor receptor: a novel target of the Wnt/β-catenin pathway in liver. Gastroenterology 129:285–302
     [Google Scholar]
132. Tauriello DVF, Palomo-Ponce S, Stork D, Berenguer-Llergo A, Badia-Ramentol J et al. 2018. TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis. Nature 554:538–43
     [Google Scholar]
133. Topalian SL, Taube JM, Anders RA, Pardoll DM 2016. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat. Rev. Cancer 16:275–87
     [Google Scholar]
134. Townsley FM, Cliffe A, Bienz M 2004. Pygopus and Legless target Armadillo/β-catenin to the nucleus to enable its transcriptional co-activator function. Nat. Cell Biol. 6:626–33
     [Google Scholar]
135. van Amerongen R, Bowman AN, Nusse R 2012. Developmental stage and time dictate the fate of Wnt/β-catenin-responsive stem cells in the mammary gland. Cell Stem Cell 11:387–400
     [Google Scholar]
136. Vermeulen L, de Sousa e Melo F, van der Heijden M, Cameron K, de Jong JH et al. 2010. Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat. Cell Biol. 12:468–76
     [Google Scholar]
137. Vermeulen L, Morrissey E, van der Heijden M, Nicholson AM, Sottoriva A et al. 2013. Defining stem cell dynamics in models of intestinal tumor initiation. Science 342:995–98
     [Google Scholar]
138. Wang B, Tian T, Kalland KH, Ke X, Qu Y 2018. Targeting Wnt/β-catenin signaling for cancer immunotherapy. Trends Pharmacol. Sci. 39:648–58
     [Google Scholar]
139. Wang B, Zhao L, Fish M, Logan CY, Nusse R 2015. Self-renewing diploid Axin2⁺ cells fuel homeostatic renewal of the liver. Nature 524:180–85
     [Google Scholar]
140. Wang K, Yuen ST, Xu J, Lee SP, Yan HH et al. 2014. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat. Genet. 46:573–82
     [Google Scholar]
141. Wei SC, Duffy CR, Allison JP 2018. Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov 8:1069–86
     [Google Scholar]
142. Winston JT, Strack P, Beer-Romero P, Chu CY, Elledge SJ, Harper JW 1999. The SCF^β-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IκBα and β-catenin and stimulates IκBα ubiquitination in vitro. Genes Dev 13:270–83
     [Google Scholar]
143. Xiao Q, Wu J, Wang WJ, Chen S, Zheng Y et al. 2018. DKK2 imparts tumor immunity evasion through β-catenin-independent suppression of cytotoxic immune-cell activation. Nat. Med. 24:262–70
     [Google Scholar]
144. Xue G, Romano E, Massi D, Mandala M 2016. Wnt/β-catenin signaling in melanoma: preclinical rationale and novel therapeutic insights. Cancer Treat. Rev. 49:1–12
     [Google Scholar]
145. Yaeger R, Chatila WK, Lipsyc MD, Hechtman JF, Cercek A et al. 2018. Clinical sequencing defines the genomic landscape of metastatic colorectal cancer. Cancer Cell 33:125–36.e3
     [Google Scholar]
146. Yan KS, Janda CY, Chang J, Zheng GXY, Larkin KA et al. 2017. Non-equivalence of Wnt and R-spondin ligands during Lgr5⁺ intestinal stem-cell self-renewal. Nature 545:238–42
     [Google Scholar]
147. Yi N, Liao QP, Li ZH, Xie BJ, Hu YH et al. 2013. RNA interference-mediated targeting of DKK1 gene expression in Ishikawa endometrial carcinoma cells causes increased tumor cell invasion and migration. Oncol. Lett. 6:756–62
     [Google Scholar]
148. Yong X, Tang B, Xiao YF, Xie R, Qin Y et al. 2016. Helicobacter pylori upregulates Nanog and Oct4 via Wnt/β-catenin signaling pathway to promote cancer stem cell-like properties in human gastric cancer. Cancer Lett 374:292–303
     [Google Scholar]
149. Yuan G, Regel I, Lian F, Friedrich T, Hitkova I et al. 2013. WNT6 is a novel target gene of caveolin-1 promoting chemoresistance to epirubicin in human gastric cancer cells. Oncogene 32:375–87
     [Google Scholar]
150. Zhang Z, Cheng L, Li J, Farah E, Atallah NM et al. 2018. Inhibition of the Wnt/β-catenin pathway overcomes resistance to enzalutamide in castration-resistant prostate cancer. Cancer Res 78:3147–62
     [Google Scholar]
151. Zhong Y, Katavolos P, Nguyen T, Lau T, Boggs J et al. 2016. Tankyrase inhibition causes reversible intestinal toxicity in mice with a therapeutic index <1. Toxicol. Pathol. 44:267–78
     [Google Scholar]
152. Zysman M, Saka A, Millar A, Knight J, Chapman W, Bapat B 2002. Methylation of Adenomatous Polyposis Coli in endometrial cancer occurs more frequently in tumors with microsatellite instability phenotype. Cancer Res 62:3663–66
     [Google Scholar]