Frizzled7: A promising achilles’ heel for targeting the Wnt receptor complex to treat cancer

Cancers

Volumn 8, Issue 5, 2016, Pages

  Phesse, Toby ^a,b,d   Flanagan, Dustin ^a   Vincan, Elizabeth ^a,c  

^a UNIVERSITY OF MELBOURNE   (Australia)

^b WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH   (Australia)

^c CURTIN UNIVERSITY   (Australia)

^d CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

Cancer; Cell signalling; Frizzled; Frizzled7; Fz7; FZD7; PCP; Receptor; Therapy; Wnt

Indexed keywords

BETA CATENIN; CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE; CALCIUM ION; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; DICKKOPF 1 PROTEIN; FRIZZLED PROTEIN; FRIZZLED7 PROTEIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MEMBRANE PROTEIN; PHOSPHOLIPASE C; PROTEIN KINASE C; PROTEIN RNF43; PROTEIN ZNRF3; R SPONDIN; SECRETED FRIZZLED RELATED PROTEIN; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG; VANTICTUMAB; WNT INHIBITORY FACTOR 1; WNT1 PROTEIN;

BINDING AFFINITY; BINDING SITE; BREAST CANCER; BREAST SARCOMA; CANCER GROWTH; CANONICAL SIGNALLING; CELL PROLIFERATION; COLORECTAL CANCER; COMPLEX FORMATION; DISEASE ASSOCIATION; DOWN REGULATION; DRUG TARGETING; ESOPHAGUS CANCER; FZD7 GENE; GENE; GENE CONTROL; GENE EXPRESSION REGULATION; HUMAN; INTESTINE CANCER; INTRACELLULAR SIGNALING; KIDNEY CANCER; LIVER CELL CARCINOMA; MELANOMA; MOLECULAR DYNAMICS; NEPHROBLASTOMA; NEUROENDOCRINE TUMOR; NON CANONICAL SIGNALLING; NON SMALL CELL LUNG CANCER; NONHUMAN; OVARY CANCER; PANCREAS CANCER; PLANAR CELL POLARITY SIGNALLING; POSTTRANSCRIPTIONAL GENE SILENCING; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; STOMACH CANCER; TUMOR INVASION; UPREGULATION; UTERINE CERVIX CANCER; WNT SIGNALING PATHWAY;

EID: 84973311142     PISSN: None     EISSN: 20726694     Source Type: Journal    
DOI: 10.3390/cancers8050050     Document Type: Review

References (237)

1. Sagara, N.; Toda, G.; Hirai, M.; Terada, M.; Katoh, M. Molecular cloning, differential expression, and chromosomal localization of human frizzled-1, frizzled-2, and frizzled-7. Biochem. Biophys. Res. Commun. 1998, 252, 117-122. [CrossRef] [PubMed]
2. Fredriksson, R.; Lagerström, M.C.; Lundin, L.G.; Schiöth, H.B. The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol. Pharmacol. 2003, 63, 1256-1272. [CrossRef] [PubMed]
3. TCGA. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012, 487, 330-337.
4. Nusse, R.; Varmus, H.E. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 1982, 31, 99-109. [CrossRef]
5. Srivastava, M.; Begovic, E.; Chapman, J.; Putnam, N.H.; Hellsten, U.; Kawashima, T.; Kuo, A.; Mitros, T.; Salamov, A.; Carpenter, M.L. et al. The Trichoplax genome and the nature of placozoans. Nature 2008, 454, 955-960. [CrossRef] [PubMed]
6. Nichols, S.A.; Dirks, W.; Pearse, J.S.; King, N. Early evolution of animal cell signaling and adhesion genes. Proc. Natl. Acad. Sci. USA 2006, 103, 12451-12456. [CrossRef] [PubMed]
7. van Amerongen, R.; Nusse, R. Towards an integrated view of Wnt signaling in development. Development 2009, 136, 3205-3214. [CrossRef] [PubMed]
8. Clevers, H.; Loh, K.M.; Nusse, R. Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control. Science 2014. [CrossRef] [PubMed]
9. Gross, J.C.; Chaudhary, V.; Bartscherer, K.; Boutros, M. Active Wnt proteins are secreted on exosomes. Nat. Cell Biol. 2012, 14, 1036-1045. [CrossRef] [PubMed]
10. Farin, H.F.; Jordens, I.; Mosa, M.H.; Basak, O.; Korving, J.; Tauriello, D.V.; de Punder, K.; Angers, S.; Peters, P.J.; Maurice, M.M. et al. Visualization of a short-range Wnt gradient in the intestinal stem-cell niche. Nature 2016, 530, 340-343. [CrossRef] [PubMed]
11. Mulligan, K.A.; Fuerer, C.; Ching, W.; Fish, M.; Willert, K.; Nusse, R. Secreted Wingless-interacting molecule (Swim) promotes long-range signaling by maintainingWingless solubility. Proc. Natl. Acad. Sci. USA 2012, 109, 370-377. [CrossRef] [PubMed]
12. Koles, K.; Budnik, V. Exosomes go with the Wnt. Cell Logist. 2012, 2, 169-173. [CrossRef] [PubMed]
13. Korkut, C.; Ataman, B.; Ramachandran, P.; Ashley, J.; Barria, R.; Gherbesi, N.; Budnik, V. Trans-synaptic transmission of vesicular Wnt signals through Evi/Wntless. Cell 2009, 139, 393-404. [CrossRef] [PubMed]
14. Niehrs, C. The complex world of WNT receptor signalling. Nat. Rev. Mol. Cell Biol. 2012, 13, 767-779. [CrossRef] [PubMed]
15. Mikels, A.J.; Nusse, R. Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context. PLoS Biol. 2006. [CrossRef] [PubMed]
16. Topol, L.; Jiang, X.; Choi, H.; Garrett-Beal, L.; Carolan, P.J.; Yang, Y. Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent beta-catenin degradation. J. Cell Biol. 2003, 162, 899-908. [CrossRef] [PubMed]
17. Ishitani, T.; Ninomiya-Tsuji, J.; Nagai, S.; Nishita, M.; Meneghini, M.; Barker, N.; Waterman, M.; Bowerman, B.; Clevers, H.; Shibuya, H. et al. The TAK1-NLK-MAPK-related pathway antagonizes signalling between beta-catenin and transcription factor TCF. Nature 1999, 399, 798-802. [PubMed]
18. Ishitani, T.; Kishida, S.; Hyodo-Miura, J.; Ueno, N.; Yasuda, J.; Waterman, M.; Shibuya, H.; Moon, R.T.; Ninomiya-Tsuji, J.; Matsumoto, K. The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca(2+) pathway to antagonize Wnt/beta-catenin signaling. Mol. Cell Biol. 2003, 23, 131-139. [CrossRef] [PubMed]
19. Kikuchi, A.; Yamamoto, H.; Sato, A.; Matsumoto, S. New insights into the mechanism of Wnt signaling pathway activation. Int. Rev. Cell Mol. Biol. 2011, 291, 21-71. [PubMed]
20. Nishita, M.; Itsukushima, S.; Nomachi, A.; Endo, M.; Wang, Z.; Inaba, D.; Qiao, S.; Takada, S.; Kikuchi, A.; Minami, Y. Ror2/Frizzled complex mediates Wnt5a-induced AP-1 activation by regulating Dishevelled polymerization. Mol. Cell Biol. 2010, 30, 3610-3619. [CrossRef] [PubMed]
21. von Maltzahn, J.; Bentzinger, C.F.; Rudnicki, M.A. Wnt7a-Fzd7 signalling directly activates the Akt/mTOR anabolic growth pathway in skeletal muscle. Nat. Cell Biol. 2012, 14, 186-191. [CrossRef] [PubMed]
22. Medina, A.; Reintsch, W.; Steinbeisser, H. Xenopus frizzled 7 can act in canonical and non-canonical Wnt signaling pathways: Implications on early patterning and morphogenesis. Mech. Dev. 2000, 92, 227-237. [CrossRef]
23. Vijayaragavan, K.; Szabo, E.; Bosse, M.; Ramos-Mejia, V.; Moon, R.T.; Bhatia, M. Noncanonical Wnt signaling orchestrates early developmental events toward hematopoietic cell fate from human embryonic stem cells. Cell Stem Cell 2009, 4, 248-262. [CrossRef] [PubMed]
24. De Calisto, J.; Araya, C.; Marchant, L.; Riaz, C.F.; Mayor, R. Essential role of non-canonical Wnt signalling in neural crest migration. Development 2005, 132, 2587-2597. [CrossRef] [PubMed]
25. Sebbagh, M.; Borg, J.P. Insight into planar cell polarity. Exp. Cell Res. 2014, 328, 284-295. [CrossRef] [PubMed]
26. Anastas, J.N.; Moon, R.T. WNT signalling pathways as therapeutic targets in cancer. Nat. Rev. Cancer 2013, 13, 11-26. [CrossRef] [PubMed]
27. Walck-Shannon, E.; Hardin, J. Cell intercalation from top to bottom. Nat. Rev. Mol. Cell Biol. 2014, 15, 34-48. [CrossRef] [PubMed]
28. Puvirajesinghe, T.M.; Bertucci, F.; Jain, A.; Scerbo, P.; Belotti, E.; Audebert, S.; Sebbagh, M.; Lopez, M.; Brech, A.; Finetti, P. et al. Identification of p62/SQSTM1 as a component of non-canonical Wnt VANGL2-JNK signalling in breast cancer. Nat. Commun. 2016. [CrossRef] [PubMed]
29. Yamaguchi, T.; Yanagisawa, K.; Sugiyama, R.; Hosono, Y.; Shimada, Y.; Arima, C.; Kato, S.; Tomida, S.; Suzuki, M.; Osada, H. et al. NKX2-1/TITF1/TTF-1-Induced ROR1 is required to sustain EGFR survival signaling in lung adenocarcinoma. Cancer Cell 2012, 21, 348-361. [CrossRef] [PubMed]
30. Zhang, S.; Chen, L.; Cui, B.; Chuang, H.Y.; Yu, J.; Wang-Rodriguez, J.; Tang, L.; Chen, G.; Basak, G.W.; Kipps, T.J. ROR1 is expressed in human breast cancer and associated with enhanced tumor-cell growth. PLoS ONE 2012, 7, e31127. [CrossRef] [PubMed]
31. Gentile, A.; Lazzari, L.; Benvenuti, S.; Trusolino, L.; Comoglio, P.M. Ror1 is a pseudokinase that is crucial for Met-driven tumorigenesis. Cancer Res. 2011, 71, 3132-3141. [CrossRef] [PubMed]
32. Rasmussen, N.R.; Debebe, Z.; Wright, T.M.; Brooks, S.A.; Sendor, A.B.; Brannon, A.R.; Hakimi, A.A.; Hsieh, J.J.; Choueiri, T.K.; Tamboli, P. et al. Expression of Ror2 mediates invasive phenotypes in renal cell carcinoma. PLoS ONE 2014, 9, e116101.
33. Slusarski, D.C.; Yang-Snyder, J.; Busa, W.B.; Moon, R.T. Modulation of embryonic intracellular Ca2+ signaling by Wnt-5A. Dev. Biol. 1997, 182, 114-120. [CrossRef] [PubMed]
34. Sheldahl, L.C.; Park, M.; Malbon, C.C.; Moon, R.T. Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in a G-protein-dependent manner. Curr. Biol. 1999, 9, 695-698. [CrossRef]
35. Kreusser, M.M.; Backs, J. Integrated mechanisms of CaMKII-dependent ventricular remodeling. Front. Pharmacol. 2014. [CrossRef] [PubMed]
36. Jones, S.E.; Jomary, C. Secreted Frizzled-related proteins: Searching for relationships and patterns. Bioessays 2002, 24, 811-820. [CrossRef] [PubMed]
37. Rehn, M.; Pihlajaniemi, T.; Hofmann, K.; Bucher, P. The frizzled motif: In how many different protein families does it occur? Trends Biochem. Sci. 1998, 23, 415-417. [CrossRef]
38. Lin, K.; Wang, S.; Julius, M.A.; Kitajewski, J.; Moos, M., Jr.; Luyten, F.P. The cysteine-rich frizzled domain of Frzb-1 is required and sufficient for modulation of Wnt signaling. Proc. Natl. Acad. Sci. USA 1997, 94, 11196-11200. [CrossRef] [PubMed]
39. Bhat, R.A.; Stauffer, B.; Komm, B.S.; Bodine, P.V. Structure-function analysis of secreted frizzled-related protein-1 for its Wnt antagonist function. J. Cell Biochem. 2007, 102, 1519-1528. [CrossRef] [PubMed]
40. Dann, C.E.; Hsieh, J.C.; Rattner, A.; Sharma, D.; Nathans, J.; Leahy, D.J. Insights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains. Nature 2001, 412, 86-90. [CrossRef] [PubMed]
41. Bafico, A.; Gazit, A.; Pramila, T.; Finch, P.W.; Yaniv, A.; Aaronson, S.A. Interaction of frizzled related protein (FRP) with Wnt ligands and the frizzled receptor suggests alternative mechanisms for FRP inhibition of Wnt signaling. J. Biol. Chem. 1999, 274, 16180-16187. [CrossRef] [PubMed]
42. Bovolenta, P.; Esteve, P.; Ruiz, J.M.; Cisneros, E.; Lopez-Rios, J. Beyond Wnt inhibition: New functions of secreted Frizzled-related proteins in development and disease. J. Cell Sci. 2008, 121, 737-746. [CrossRef] [PubMed]
43. Xavier, C.P.; Melikova, M.; Chuman, Y.; Uren, A.; Baljinnyam, B.; Rubin, J.S. Secreted Frizzled-related protein potentiation versus inhibition of Wnt3a/beta-catenin signaling. Cell Signal. 2014, 26, 94-101. [CrossRef] [PubMed]
44. Wawrzak, D.; Metioui, M.; Willems, E.; Hendrickx, M.; de Genst, E.; Leyns, L. Wnt3a binds to several sFRPs in the nanomolar range. Biochem. Biophys. Res. Commun. 2007, 357, 1119-1123. [CrossRef] [PubMed]
45. Galli, L.M.; Barnes, T.; Cheng, T.; Acosta, L.; Anglade, A.; Willert, K.; Nusse, R.; Burrus, L.W. Differential inhibition of Wnt-3a by Sfrp-1, Sfrp-2, and Sfrp-3. Dev. Dyn. 2006, 235, 681-690. [CrossRef] [PubMed]
46. von Marschall, Z.; Fisher, L.W. Secreted Frizzled-related protein-2 (sFRP2) augments canonical Wnt3a-induced signaling. Biochem. Biophys. Res. Commun. 2010, 400, 299-304. [CrossRef] [PubMed]
47. Hsieh, J.C.; Kodjabachian, L.; Rebbert, M.L.; Rattner, A.; Smallwood, P.M.; Samos, C.H.; Nusse, R.; Dawid, I.B.; Nathans, J. A new secreted protein that binds to Wnt proteins and inhibits their activities. Nature 1999, 398, 431-436. [PubMed]
48. Malinauskas, T.; Aricescu, A.R.; Lu, W.; Siebold, C.; Jones, E.Y. Modular mechanism of Wnt signaling inhibition by Wnt inhibitory factor 1. Nat. Struct. Mol. Biol. 2011, 18, 886-893. [CrossRef] [PubMed]
49. MacDonald, B.T.; Adamska, M.; Meisler, M.H. Hypomorphic expression of Dkk1 in the doubleridge mouse: Dose dependence and compensatory interactions with Lrp6. Development 2004, 131, 2543-2552. [CrossRef] [PubMed]
50. Niehrs, C. Function and biological roles of the Dickkopf family of Wnt modulators. Oncogene 2006, 25, 7469-7481. [CrossRef] [PubMed]
51. Pinto, D.; Gregorieff, A.; Begthel, H.; Clevers, H. Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. Genes Dev. 2003, 17, 1709-1713. [CrossRef] [PubMed]
52. Kuhnert, F.; Davis, C.R.; Wang, H.T.; Chu, P.; Lee, M.; Yuan, J.; Nusse, R.; Kuo, C.J. Essential requirement for Wnt signaling in proliferation of adult small intestine and colon revealed by adenoviral expression of Dickkopf-1. Proc. Natl. Acad. Sci. USA 2004, 101, 266-271. [CrossRef] [PubMed]
53. Kim, K.A.; Wagle, M.; Tran, K.; Zhan, X.; Dixon, M.A.; Liu, S.; Gros, D.; Korver, W.; Yonkovich, S.; Tomasevic, N. et al. R-Spondin family members regulate the Wnt pathway by a common mechanism. Mol. Biol. Cell 2008, 19, 2588-2596. [CrossRef] [PubMed]
54. Schuijers, J.; Clevers, H. Adult mammalian stem cells: The role of Wnt, Lgr5 and R-spondins. Embo. J. 2012, 31, 2685-2696. [CrossRef] [PubMed]
55. de Lau, W.; Barker, N.; Low, T.Y.; Koo, B.K.; Li, V.S.; Teunissen, H.; Kujala, P.; Haegebarth, A.; Peters, P.J.; van de Wetering, M. et al. Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature 2011, 476, 293-297. [CrossRef] [PubMed]
56. Carmon, K.S.; Gong, X.; Lin, Q.; Thomas, A.; Liu, Q. R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling. Proc. Natl. Acad. Sci. USA 2011, 108, 11452-11457. [CrossRef] [PubMed]
57. Hao, H.X.; Xie, Y.; Zhang, Y.; Charlat, O.; Oster, E.; Avello, M.; Lei, H.; Mickanin, C.; Liu, D.; Ruffner, H. et al. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature 2012, 485, 195-200. [CrossRef] [PubMed]
58. Koo, B.K.; Spit, M.; Jordens, I.; Low, T.Y.; Stange, D.E.; van de Wetering, M.; van Es, J.H.; Mohammed, S.; Heck, A.J.; Maurice, M.M. et al. Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature 2012, 488, 665-669. [CrossRef] [PubMed]
59. Peng, W.C.; de Lau, W.; Madoori, P.K.; Forneris, F.; Granneman, J.C.; Clevers, H.; Gros, P. Structures of Wnt-antagonist ZNRF3 and its complex with R-spondin 1 and implications for signaling. PLoS ONE 2013, 8, e83110. [CrossRef] [PubMed]
60. Ohkawara, B.; Glinka, A.; Niehrs, C. Rspo3 binds syndecan 4 and induces Wnt/PCP signaling via clathrin-mediated endocytosis to promote morphogenesis. Developmental. Cell 2011, 20, 303-314. [CrossRef] [PubMed]
61. Bhanot, P.; Brink, M.; Samos, C.H.; Hsieh, J.C.; Wang, Y.; Macke, J.P.; Andrew, D.; Nathans, J.; Nusse, R. A new member of the frizzled family from Drosophila functions as aWingless receptor. Nature 1996, 382, 225-230. [CrossRef] [PubMed]
62. Flanagan, D.J.; Phesse, T.J.; Barker, N.; Schwab, R.H.; Amin, N.; Malaterre, J.; Stange, D.E.; Nowell, C.J.; Currie, S.A.; Saw, J.T. et al. Frizzled7 functions as a Wnt receptor in intestinal epithelial Lgr5(+) stem cells. Stem Cell Reports 2015, 4, 759-767. [CrossRef] [PubMed]
63. Kim, M.; Lee, H.C.; Tsedensodnom, O.; Hartley, R.; Lim, Y.S.; Yu, E.; Merle, P.; Wands, J.R. Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/beta-catenin signaling pathway in hepatocellular carcinoma cells. J. Hepatol. 2008, 48, 780-791. [CrossRef] [PubMed]
64. Matsumoto, K.; Miki, R.; Nakayama, M.; Tatsumi, N.; Yokouchi, Y. Wnt9a secreted from the walls of hepatic sinusoids is essential for morphogenesis, proliferation, and glycogen accumulation of chick hepatic epithelium. Dev. Biol. 2008, 319, 234-247. [CrossRef] [PubMed]
65. Kaykas, A.; Yang-Snyder, J.; Heroux, M.; Shah, K.V.; Bouvier, M.; Moon, R.T. Mutant Frizzled 4 associated with vitreoretinopathy traps wild-type Frizzled in the endoplasmic reticulum by oligomerization. Nat. Cell Biol. 2004, 6, 52-58. [CrossRef] [PubMed]
66. Dufourcq, P.; Leroux, L.; Ezan, J.; Descamps, B.; Lamaziere, J.M.; Costet, P.; Basoni, C.; Moreau, C.; Deutsch, U.; Couffinhal, T. et al. Regulation of endothelial cell cytoskeletal reorganization by a secreted frizzled-related protein-1 and frizzled 4-and frizzled 7-dependent pathway: Role in neovessel formation. Am. J. Pathol. 2008, 172, 37-49. [CrossRef] [PubMed]
67. Kim, G.H.; Her, J.H.; Han, J.K. Ryk cooperates with Frizzled 7 to promote Wnt11-mediated endocytosis and is essential for Xenopus laevis convergent extension movements. J. Cell Biol. 2008, 182, 1073-1082. [CrossRef] [PubMed]
68. Hering, H.; Sheng, M. Direct interaction of Frizzled-1,-2,-4, and-7 with PDZ domains of PSD-95. FEBS Lett. 2002, 521, 185-189. [CrossRef]
69. Yao, R.; Natsume, Y.; Noda, T. MAGI-3 is involved in the regulation of the JNK signaling pathway as a scaffold protein for frizzled and Ltap. Oncogene 2004, 23, 6023-6030. [CrossRef] [PubMed]
70. James, R.G.; Bosch, K.A.; Kulikauskas, R.M.; Yang, P.T.; Robin, N.C.; Toroni, R.A.; Biechele, T.L.; Berndt, J.D.; von Haller, P.D.; Eng, J.K. et al. Protein kinase PKN1 represses Wnt/beta-catenin signaling in human melanoma cells. J. Biol. Chem. 2013, 288, 34658-34670. [CrossRef] [PubMed]
71. Nichols, A.S.; Floyd, D.H.; Bruinsma, S.P.; Narzinski, K.; Baranski, T.J. Frizzled receptors signal through G proteins. Cell Signal. 2013, 25, 1468-1475. [CrossRef] [PubMed]
72. Giles, R.H.; van Es, J.H.; Clevers, H. Caught up in a Wnt storm: Wnt signaling in cancer. Biochim. Biophys. Acta 2003, 1653, 1-24. [CrossRef]
73. Polakis, P. Wnt signaling in cancer. Cold Spring Harb. Perspect. Biol. 2012. [CrossRef] [PubMed]
74. Albuquerque, C.; Breukel, C.; van der Luijt, R.; Fidalgo, P.; Lage, P.; Slors, F.J.; Leitao, C.N.; Fodde, R.; Smits, R. The “just-right” signaling model: APC somatic mutations are selected based on a specific level of activation of the beta-catenin signaling cascade. Hum. Mol. Genet. 2002, 11, 1549-1560. [CrossRef] [PubMed]
75. Su, L.K.; Kinzler, K.W.; Vogelstein, B.; Preisinger, A.C.; Moser, A.R.; Luongo, C.; Gould, K.A.; Dove, W.F. Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 1992, 256, 668-670. [CrossRef] [PubMed]
76. Pollard, P.; Deheragoda, M.; Segditsas, S.; Lewis, A.; Rowan, A.; Howarth, K.; Willis, L.; Nye, E.; McCart, A.; Mandir, N. et al. The Apc 1322T mouse develops severe polyposis associated with submaximal nuclear beta-catenin expression. Gastroenterology 2009, 136, 2204-2213. [CrossRef] [PubMed]
77. Meniel, V.; Song, F.; Phesse, T.; Young, M.; Poetz, O.; Parry, L.; Jenkins, J.R.; Williams, G.T.; Dunwoodie, S.L.; Watson, A. et al. Cited1 deficiency suppresses intestinal tumorigenesis. PLoS Genet. 2013. [CrossRef] [PubMed]
78. Sansom, O.J.; Meniel, V.S.; Muncan, V.; Phesse, T.J.; Wilkins, J.A.; Reed, K.R.; Vass, J.K.; Athineos, D.; Clevers, H.; Clarke, A.R. Myc deletion rescues Apc deficiency in the small intestine. Nature 2007, 446, 676-679. [CrossRef] [PubMed]
79. Suzuki, H.; Watkins, D.N.; Jair, K.W.; Schuebel, K.E.; Markowitz, S.D.; Chen, W.D.; Pretlow, T.P.; Yang, B.; Akiyama, Y.; Van Engeland, M. et al. Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat. Genet. 2004, 36, 417-422. [CrossRef] [PubMed]
80. Caldwell, G.M.; Jones, C.; Gensberg, K.; Jan, S.; Hardy, R.G.; Byrd, P.; Chughtai, S.; Wallis, Y.; Matthews, G.M.; Morton, D.G. The Wnt antagonist sFRP1 in colorectal tumorigenesis. Cancer Res. 2004, 64, 883-888. [CrossRef] [PubMed]
81. Cheng, Y.Y.; Yu, J.; Wong, Y.P.; Man, E.P.; To, K.F.; Jin, V.X.; Li, J.; Tao, Q.; Sung, J.J.; Chan, F.K. et al. Frequent epigenetic inactivation of secreted frizzled-related protein 2 (SFRP2) by promoter methylation in human gastric cancer. Br. J. Cancer 2007, 97, 895-901. [CrossRef] [PubMed]
82. Mazieres, J.; He, B.; You, L.; Xu, Z.; Lee, A.Y.; Mikami, I.; Reguart, N.; Rosell, R.; McCormick, F.; Jablons, D.M. Wnt inhibitory factor-1 is silenced by promoter hypermethylation in human lung cancer. Cancer Res. 2004, 64, 4717-4720. [CrossRef] [PubMed]
83. Zhang, X.; Lu, Z.X.; Sheng, Y.H.; Wu, X.B.; Gao, J.; Zhao, W.H.; Tao, H.M. [Closed reduction and micro-incision for the treatment of distal tibia fractures]. Zhongguo Gu Shang 2010, 23, 717-718. [PubMed]
84. Vincan, E.; Darcy, P.K.; Smyth, M.J.; Thompson, E.W.; Thomas, R.J.; Phillips, W.A.; Ramsay, R.G. Frizzled-7 receptor ectodomain expression in a colon cancer cell line induces morphological change and attenuates tumor growth. Differentiation 2005, 73, 142-153. [CrossRef] [PubMed]
85. Vermeulen, L.; De Sousa, E.M.; van der Heijden, M.; Cameron, K.; de Jong, J.H.; Borovski, T.; Tuynman, J.B.; Todaro, M.; Merz, C.; Rodermond, H. et al. Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat. Cell Biol. 2010, 12, 468-476. [CrossRef] [PubMed]
86. Dimitriadis, A.; Vincan, E.; Mohammed, I.M.; Roczo, N.; Phillips, W.A.; Baindur-Hudson, S. Expression of Wnt genes in human colon cancers. Cancer Lett. 2001, 166, 185-191. [CrossRef]
87. Willert, J.; Epping, M.; Pollack, J.R.; Brown, P.O.; Nusse, R. A transcriptional response to Wnt protein in human embryonic carcinoma cells. BMC Dev. Biol. 2002, 2, 8. [CrossRef] [PubMed]
88. Vincan, E.; Flanagan, D.J.; Pouliot, N.; Brabletz, T.; Spaderna, S. Variable FZD7 expression in colorectal cancers indicates regulation by the tumour microenvironment. Dev. Dyn. 2010, 239, 311-317. [CrossRef] [PubMed]
89. Vinson, C.R.; Adler, P.N. Directional non-cell autonomy and the transmission of polarity information by the frizzled gene of Drosophila. Nature 1987, 329, 549-551. [CrossRef] [PubMed]
90. Adler, P.N.; Vinson, C.; Park, W.J.; Conover, S.; Klein, L. Molecular structure of frizzled, a Drosophila tissue polarity gene. Genetics 1990, 126, 401-416. [PubMed]
91. Adell, T.; Nefkens, I.; Muller, W.E. Polarity factor 'Frizzled' in the demosponge Suberites domuncula: Identification, expression and localization of the receptor in the epithelium/pinacoderm(1). FEBS Lett. 2003, 554, 363-368. [CrossRef]
92. Minobe, S.; Fei, K.; Yan, L.; Sarras, M., Jr.; Werle, M. Identification and characterization of the epithelial polarity receptor "Frizzled" in Hydra vulgaris. Dev. Genes Evol. 2000, 210, 258-262. [CrossRef] [PubMed]
93. Wang, Y.; Macke, J.P.; Abella, B.S.; Andreasson, K.; Worley, P.; Gilbert, D.J.; Copeland, N.G.; Jenkins, N.A.; Nathans, J. A large family of putative transmembrane receptors homologous to the product of the Drosophila tissue polarity gene frizzled. J. Biol. Chem. 1996, 271, 4468-4476. [PubMed]
94. Yang-Snyder, J.; Miller, J.R.; Brown, J.D.; Lai, C.J.; Moon, R.T. A frizzled homolog functions in a vertebrate Wnt signaling pathway. Curr. Biol. 1996, 6, 1302-1306. [CrossRef]
95. Tanaka, S.; Akiyoshi, T.; Mori, M.; Wands, J.R.; Sugimachi, K. A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals. Proc. Natl. Acad. Sci. USA 1998, 95, 10164-10169. [CrossRef] [PubMed]
96. Wheeler, G.N.; Hoppler, S. Two novel Xenopus frizzled genes expressed in developing heart and brain. Mech. Dev. 1999, 86, 203-207. [CrossRef]
97. Abu-Elmagd, M.; Garcia-Morales, C.; Wheeler, G.N. Frizzled7 mediates canonical Wnt signaling in neural crest induction. Dev. Biol. 2006, 298, 285-298. [CrossRef] [PubMed]
98. Winklbauer, R.; Medina, A.; Swain, R.K.; Steinbeisser, H. Frizzled-7 signalling controls tissue separation during Xenopus gastrulation. Nature 2001, 413, 856-860. [CrossRef] [PubMed]
99. Hobmayer, E.; Hatta, M.; Fischer, R.; Fujisawa, T.; Holstein, T.W.; Sugiyama, T. Identification of a Hydra homologue of the beta-catenin/plakoglobin/armadillo gene family. Gene 1996, 172, 155-159. [CrossRef]
100. Technau, U.; Rudd, S.; Maxwell, P.; Gordon, P.M.; Saina, M.; Grasso, L.C.; Hayward, D.C.; Sensen, C.W.; Saint, R.; Holstein, T.W. et al. Maintenance of ancestral complexity and non-metazoan genes in two basal cnidarians. Trends Genet. 2005, 21, 633-639. [CrossRef] [PubMed]
101. Lee, P.N.; Pang, K.; Matus, D.Q.; Martindale, M.Q. A WNT of things to come: evolution of Wnt signaling and polarity in cnidarians. Semin. Cell Dev. Biol. 2006, 17, 157-167. [CrossRef] [PubMed]
102. Wikramanayake, A.H.; Hong, M.; Lee, P.N.; Pang, K.; Byrum, C.A.; Bince, J.M.; Xu, R.; Martindale, M.Q. An ancient role for nuclear beta-catenin in the evolution of axial polarity and germ layer segregation. Nature 2003, 426, 446-450. [CrossRef] [PubMed]
103. Hobmayer, B.; Rentzsch, F.; Kuhn, K.; Happel, C.M.; von Laue, C.C.; Snyder, P.; Rothbacher, U.; Holstein, T.W. WNT signalling molecules act in axis formation in the diploblastic metazoan Hydra. Nature 2000, 407, 186-189. [CrossRef] [PubMed]
104. Guder, C.; Pinho, S.; Nacak, T.G.; Schmidt, H.A.; Hobmayer, B.; Niehrs, C.; Holstein, T.W. An ancient Wnt-Dickkopf antagonism in Hydra. Development 2006, 133, 901-911. [CrossRef] [PubMed]
105. Guder, C.; Philipp, I.; Lengfeld, T.; Watanabe, H.; Hobmayer, B.; Holstein, T.W. The Wnt code: Cnidarians signal the way. Oncogene 2006, 25, 7450-7460. [CrossRef] [PubMed]
106. Vincan, E. Frizzled/WNT signalling: The insidious promoter of tumour growth and progression. Front. Biosci. 2004, 9, 1023-1034. [CrossRef] [PubMed]
107. Sumanas, S.; Strege, P.; Heasman, J.; Ekker, S.C. The putative wnt receptor Xenopus frizzled-7 functions upstream of beta-catenin in vertebrate dorsoventral mesoderm patterning. Development 2000, 127, 1981-1990. [PubMed]
108. Korinek, V.; Barker, N.; Moerer, P.; van Donselaar, E.; Huls, G.; Peters, P.J.; Clevers, H. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat. Genet. 1998, 19, 379-383. [PubMed]
109. van de Wetering, M.; Sancho, E.; Verweij, C.; de Lau, W.; Oving, I.; Hurlstone, A.; van der Horn, K.; Batlle, E.; Coudreuse, D.; Haramis, A.P. et al. The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 2002, 111, 241-250. [CrossRef]
110. Gregorieff, A.; Pinto, D.; Begthel, H.; Destree, O.; Kielman, M.; Clevers, H. Expression pattern of Wnt signaling components in the adult intestine. Gastroenterology 2005, 129, 626-638. [CrossRef] [PubMed]
111. Yu, H.; Ye, X.; Guo, N.; Nathans, J. Frizzled 2 and frizzled 7 function redundantly in convergent extension and closure of the ventricular septum and palate: Evidence for a network of interacting genes. Development 2012, 139, 4383-4394. [CrossRef] [PubMed]
112. Kibar, Z.; Vogan, K.J.; Groulx, N.; Justice, M.J.; Underhill, D.A.; Gros, P. Ltap, a mammalian homolog of Drosophila Strabismus/Van Gogh, is altered in the mouse neural tube mutant Loop-tail. Nat. Genet. 2001, 28, 251-255. [CrossRef] [PubMed]
113. Curtin, J.A.; Quint, E.; Tsipouri, V.; Arkell, R.M.; Cattanach, B.; Copp, A.J.; Henderson, D.J.; Spurr, N.; Stanier, P.; Fisher, E.M. et al. Murdoch Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse. Curr. Biol. 2003, 13, 1129-1133. [CrossRef]
114. Paudyal, A.; Damrau, C.; Patterson, V.L.; Ermakov, A.; Formstone, C.; Lalanne, Z.; Wells, S.; Lu, X.; Norris, D.P.; Dean, C.H. et al. The novel mouse mutant, chuzhoi, has disruption of Ptk7 protein and exhibits defects in neural tube, heart and lung development and abnormal planar cell polarity in the ear. BMC Dev. Biol. 2010. [CrossRef] [PubMed]
115. Zarbalis, K.; May, S.R.; Shen, Y.; Ekker, M.; Rubenstein, J.L.; Peterson, A.S. A focused and efficient genetic screening strategy in the mouse: Identification of mutations that disrupt cortical development. PLoS Biol. 2004. [CrossRef] [PubMed]
116. Muncan, V.; Sansom, O.J.; Tertoolen, L.; Phesse, T.J.; Begthel, H.; Sancho, E.; Cole, A.M.; Gregorieff, A.; de Alboran, I.M.; Clevers, H. et al. Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target gene c-Myc. Mol. Cell Biol. 2006, 26, 8418-8426. [CrossRef] [PubMed]
117. Greenow, K.R.; Clarke, A.R.; Jones, R.H. Chk1 deficiency in the mouse small intestine results in p53-independent crypt death and subsequent intestinal compensation. Oncogene 2009, 28, 1443-1453. [CrossRef] [PubMed]
118. Huang, H.C.; Klein, P.S. The Frizzled family: Receptors for multiple signal transduction pathways. Genome Biol. 2004. [CrossRef]
119. de Lau, W.; Peng, W.C.; Gros, P.; Clevers, H. The R-spondin/Lgr5/Rnf43 module: Regulator of Wnt signal strength. Genes Dev. 2014, 28, 305-316. [CrossRef] [PubMed]
120. Linker, C.; Lesbros, C.; Gros, J.; Burrus, L.W.; Rawls, A.; Marcelle, C. beta-Catenin-dependent Wnt signalling controls the epithelial organisation of somites through the activation of paraxis. Development 2005, 132, 3895-3905. [CrossRef] [PubMed]
121. Wu, J.; Klein, T.J.; Mlodzik, M. Subcellular localization of frizzled receptors, mediated by their cytoplasmic tails, regulates signaling pathway specificity. PLoS Biol. 2004. [CrossRef] [PubMed]
122. Sato, T.; van Es, J.H.; Snippert, H.J.; Stange, D.E.; Vries, R.G.; van den Born, M.; Barker, N.; Shroyer, N.F.; van de Wetering, M.; Clevers, H. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 2011, 469, 415-418. [CrossRef] [PubMed]
123. Flanagan, D.; Phesse, T.; Vincan, E.; Doherty Institute, University of Melbourne, Melbourne, VIC 3000, Australia. Unpublished data. 2016.
124. Zhang, Z.; Rankin, S.A.; Zorn, A.M. Different thresholds of Wnt-Frizzled 7 signaling coordinate proliferation, morphogenesis and fate of endoderm progenitor cells. Dev. Biol. 2013, 378, 1-12. [CrossRef] [PubMed]
125. Assou, S.; Le Carrour, T.; Tondeur, S.; Strom, S.; Gabelle, A.; Marty, S.; Nadal, L.; Pantesco, V.; Reme, T.; Hugnot, J.P. et al. A meta-analysis of human embryonic stem cells transcriptome integrated into a web-based expression atlas. Stem Cells 2007, 25, 961-973. [CrossRef] [PubMed]
126. Dormeyer, W.; van Hoof, D.; Braam, S.R.; Heck, A.J.; Mummery, C.L.; Krijgsveld, J. Plasma membrane proteomics of human embryonic stem cells and human embryonal carcinoma cells. J. Proteome Res. 2008, 7, 2936-2951. [CrossRef] [PubMed]
127. Melchior, K.; Weiss, J.; Zaehres, H.; Kim, Y.M.; Lutzko, C.; Roosta, N.; Hescheler, J.; Muschen, M. The WNT receptor FZD7 contributes to self-renewal signaling of human embryonic stem cells. Biol. Chem. 2008, 389, 897-903. [CrossRef] [PubMed]
128. Fernandez, A.; Huggins, I.J.; Perna, L.; Brafman, D.; Lu, D.; Yao, S.; Gaasterland, T.; Carson, D.A.; Willert, K. The WNT receptor FZD7 is required for maintenance of the pluripotent state in human embryonic stem cells. Proc. Natl. Acad. Sci. USA 2014, 111, 1409-1414. [CrossRef] [PubMed]
129. Janda, C.Y.; Waghray, D.; Levin, A.M.; Thomas, C.; Garcia, K.C. Structural basis of Wnt recognition by Frizzled. Science 2012, 337, 59-64. [CrossRef] [PubMed]
130. Umbhauer, M.; Djiane, A.; Goisset, C.; Penzo-Mendez, A.; Riou, J.F.; Boucaut, J.C.; Shi, D.L. The C-terminal cytoplasmic Lys-thr-X-X-X-Trp motif in frizzled receptors mediates Wnt/beta-catenin signalling. Embo. J. 2000, 19, 4944-4954. [CrossRef] [PubMed]
131. Djiane, A.; Riou, J.; Umbhauer, M.; Boucaut, J.; Shi, D. Role of frizzled 7 in the regulation of convergent extension movements during gastrulation in Xenopus laevis. Development 2000, 127, 3091-3100. [PubMed]
132. Weeraratna, A.T.; Jiang, Y.; Hostetter, G.; Rosenblatt, K.; Duray, P.; Bittner, M.; Trent, J.M. Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell 2002, 1, 279-288. [CrossRef]
133. Van Raay, T.J.; Moore, K.B.; Iordanova, I.; Steele, M.; Jamrich, M.; Harris, W.A.; Vetter, M.L. Frizzled 5 signaling governs the neural potential of progenitors in the developing Xenopus retina. Neuron 2005, 46, 23-36. [CrossRef] [PubMed]
134. Ohba, S.; Lanigan, T.M.; Roessler, B.J. Leptin receptor JAK2/STAT3 signaling modulates expression of Frizzled receptors in articular chondrocytes. Osteoarthritis Cartilage 2010, 18, 1620-1629. [CrossRef] [PubMed]
135. Bhat, V.; Sun, Y.J.; Weger, S.; Raouf, A. Notch-Induced Expression of FZD7 Requires Noncanonical NOTCH3 Signaling in Human Breast Epithelial Cells. Stem Cells Dev. 2016, 25, 522-529. [CrossRef] [PubMed]
136. Sweetman, D.; Goljanek, K.; Rathjen, T.; Oustanina, S.; Braun, T.; Dalmay, T.; Munsterberg, A. Specific requirements of MRFs for the expression of muscle specific microRNAs, miR-1, miR-206 and miR-133. Dev. Biol. 2008, 321, 491-499. [CrossRef] [PubMed]
137. Goljanek-Whysall, K.; Pais, H.; Rathjen, T.; Sweetman, D.; Dalmay, T.; Munsterberg, A. Regulation of multiple target genes by miR-1 and miR-206 is pivotal for C2C12 myoblast differentiation. J. Cell Sci. 2012, 125, 3590-3600. [CrossRef] [PubMed]
138. Ashton, G.H.; Morton, J.P.; Myant, K.; Phesse, T.J.; Ridgway, R.A.; Marsh, V.; Wilkins, J.A.; Athineos, D.; Muncan, V.; Kemp, R. et al. Focal adhesion kinase is required for intestinal regeneration and tumorigenesis downstream of Wnt/c-Myc signaling. Developmental Cell 2010, 19, 259-269. [CrossRef] [PubMed]
139. Liu, S.; Sun, X.; Wang, M.; Hou, Y.; Zhan, Y.; Jiang, Y.; Liu, Z.; Cao, X.; Chen, P.; Chen, X. et al. A microRNA 221-and 222-mediated feedback loop maintains constitutive activation of NFkappaB and STAT3 in colorectal cancer cells. Gastroenterology 2014, 147, 847-859. [CrossRef] [PubMed]
140. Chung, H.K.; Chen, Y.; Rao, J.N.; Liu, L.; Xiao, L.; Turner, D.J.; Yang, P.; Gorospe, M.; Wang, J.Y. Transgenic Expression of miR-222 disrupts intestinal epithelial regeneration by targeting multiple genes including Frizzled-7. Mol. Med. 2015. [CrossRef] [PubMed]
141. Li, Z.; Chen, P.; Su, R.; Li, Y.; Hu, C.; Wang, Y.; Arnovitz, S.; He, M.; Gurbuxani, S.; Zuo, Z. et al. Overexpression and knockout of miR-126 both promote leukemogenesis. Blood 2015, 126, 2005-2015. [CrossRef] [PubMed]
142. Groden, J.; Thliveris, A.; Samowitz, W.; Carlson, M.; Gelbert, L.; Albertsen, H.; Joslyn, G.; Stevens, J.; Spirio, L.; Robertson, M. et al. Identification and characterization of the familial adenomatous polyposis coli gene. Cell 1991, 66, 589-600. [CrossRef]
143. Nishisho, I.; Nakamura, Y.; Miyoshi, Y.; Miki, Y.; Ando, H.; Horii, A.; Koyama, K.; Utsunomiya, J.; Baba, S.; Hedge, P. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 1991, 253, 665-669. [CrossRef] [PubMed]
144. Kinzler, K.W.; Vogelstein, B. Lessons from hereditary colorectal cancer. Cell 1996, 87, 159-170. [CrossRef]
145. Moser, A.R.; Pitot, H.C.; Dove, W.F. A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science 1990, 247, 322-324. [CrossRef] [PubMed]
146. Shibata, H.; Toyama, K.; Shioya, H.; Ito, M.; Hirota, M.; Hasegawa, S.; Matsumoto, H.; Takano, H.; Akiyama, T.; Toyoshima, K. et al. Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene. Science 1997, 278, 120-123. [CrossRef] [PubMed]
147. Sansom, O.J.; Reed, K.R.; Hayes, A.J.; Ireland, H.; Brinkmann, H.; Newton, I.P.; Batlle, E.; Simon-Assmann, P.; Clevers, H.; Nathke, I.S. et al. Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration. Genes Dev. 2004, 18, 1385-1390. [CrossRef] [PubMed]
148. Barker, N.; Ridgway, R.A.; van Es, J.H.; van deWetering, M.; Begthel, H.; van den Born, M.; Danenberg, E.; Clarke, A.R.; Sansom, O.J.; Clevers, H. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 2009, 457, 608-611. [CrossRef] [PubMed]
149. Harada, N.; Tamai, Y.; Ishikawa, T.; Sauer, B.; Takaku, K.; Oshima, M.; Taketo, M.M. Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene. Embo. J. 1999, 18, 5931-5942. [CrossRef] [PubMed]
150. Ireland, H.; Kemp, R.; Houghton, C.; Howard, L.; Clarke, A.R.; Sansom, O.J.; Winton, D.J. Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: Effect of loss of beta-catenin. Gastroenterology 2004, 126, 1236-1246. [CrossRef] [PubMed]
151. Clevers, H.; Nusse, R. Wnt/beta-catenin signaling and disease. Cell 2012, 149, 1192-1205. [CrossRef] [PubMed]
152. Vincan, E.; Barker, N. The upstream components of the Wnt signalling pathway in the dynamic EMT and MET associated with colorectal cancer progression. Clin. Exp. Metastasis 2008, 25, 657-663. [CrossRef] [PubMed]
153. Faux, M.C.; Ross, J.L.; Meeker, C.; Johns, T.; Ji, H.; Simpson, R.J.; Layton, M.J.; Burgess, A.W. Restoration of full-length adenomatous polyposis coli (APC) protein in a colon cancer cell line enhances cell adhesion. J. Cell Sci. 2004, 117, 427-439. [CrossRef] [PubMed]
154. Dow, L.E.; O’Rourke, K.P.; Simon, J.; Tschaharganeh, D.F.; van Es, J.H.; Clevers, H.; Lowe, S.W. Apc Restoration promotes cellular differentiation and reestablishes crypt homeostasis in colorectal cancer. Cell 2015, 161, 1539-1552. [CrossRef] [PubMed]
155. Aguilera, O.; Fraga, M.F.; Ballestar, E.; Paz, M.F.; Herranz, M.; Espada, J.; Garcia, J.M.; Munoz, A.; Esteller, M.; Gonzalez-Sancho, J.M. Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 (DKK-1) gene in human colorectal cancer. Oncogene 2006, 25, 4116-4121. [CrossRef] [PubMed]
156. Seshagiri, S.; Stawiski, E.W.; Durinck, S.; Modrusan, Z.; Storm, E.E.; Conboy, C.B.; Chaudhuri, S.; Guan, Y.; Janakiraman, V.; Jaiswal, B.S. et al. Recurrent R-spondin fusions in colon cancer. Nature 2012, 488, 660-664. [CrossRef] [PubMed]
157. Chartier, C.; Raval, J.; Axelrod, F.; Bond, C.; Cain, J.; Dee-Hoskins, C.; Ma, S.; Fischer, M.M.; Shah, J.; Wei, J. et al. Therapeutic targeting of tumor-derived R-spondin attenuates beta-catenin signaling and tumorigenesis in multiple cancer types. Cancer Res. 2016, 76, 713-723. [CrossRef] [PubMed]
158. Vincan, E.; Darcy, P.K.; Farrelly, C.A.; Faux, M.C.; Brabletz, T.; Ramsay, R.G. Frizzled-7 dictates three-dimensional organization of colorectal cancer cell carcinoids. Oncogene 2007, 26, 2340-2352. [CrossRef] [PubMed]
159. Qi, J.; Yu, Y.; Akilli Ozturk, O.; Holland, J.D.; Besser, D.; Fritzmann, J.; Wulf-Goldenberg, A.; Eckert, K.; Fichtner, I.; Birchmeier, W. New Wnt/beta-catenin target genes promote experimental metastasis and migration of colorectal cancer cells through different signals. Gut 2015. [CrossRef]
160. Brabletz, T.; Jung, A.; Reu, S.; Porzner, M.; Hlubek, F.; Kunz-Schughart, L.A.; Knuechel, R.; Kirchner, T. Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc. Natl. Acad. Sci. USA 2001, 98, 10356-10361. [CrossRef] [PubMed]
161. Thiery, J.P.; Acloque, H.; Huang, R.Y.; Nieto, M.A. Epithelial-mesenchymal transitions in development and disease. Cell 2009, 139, 871-890. [CrossRef] [PubMed]
162. Vincan, E.; Brabletz, T.; Faux, M.C.; Ramsay, R.G. A human three-dimensional cell line model allows the study of dynamic and reversible epithelial-mesenchymal and mesenchymal-epithelial transition that underpins colorectal carcinogenesis. Cells Tissues Organs 2007, 185, 20-28. [CrossRef] [PubMed]
163. Christofori, G. New signals from the invasive front. Nature 2006, 441, 444-450. [CrossRef] [PubMed]
164. Ueno, K.; Hazama, S.; Mitomori, S.; Nishioka, M.; Suehiro, Y.; Hirata, H.; Oka, M.; Imai, K.; Dahiya, R.; Hinoda, Y. Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells. Br. J. Cancer 2009, 101, 1374-1381. [CrossRef] [PubMed]
165. Zhang, H.; Hao, Y.; Yang, J.; Zhou, Y.; Li, J.; Yin, S.; Sun, C.; Ma, M.; Huang, Y.; Xi, J.J. Genome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis. Nat. Commun. 2011. [CrossRef] [PubMed]
166. Wong, C.M.; Fan, S.T.; Ng, I.O. beta-Catenin mutation and overexpression in hepatocellular carcinoma: clinicopathologic and prognostic significance. Cancer 2001, 92, 136-145. [CrossRef]
167. Merle, P.; de la Monte, S.; Kim, M.; Herrmann, M.; Tanaka, S.; Von Dem Bussche, A.; Kew, M.C.; Trepo, C.; Wands, J.R. Functional consequences of frizzled-7 receptor overexpression in human hepatocellular carcinoma. Gastroenterology 2004, 127, 1110-1122. [CrossRef] [PubMed]
168. Pez, F.; Lopez, A.; Kim, M.; Wands, J.R.; Caron de Fromentel, C.; Merle, P. Wnt signaling and hepatocarcinogenesis: Molecular targets for the development of innovative anticancer drugs. J. Hepatol. 2013, 59, 1107-1117. [CrossRef] [PubMed]
169. Shen, Q.; Fan, J.; Yang, X.R.; Tan, Y.; Zhao, W.; Xu, Y.; Wang, N.; Niu, Y.; Wu, Z.; Zhou, J. et al. Serum DKK1 as a protein biomarker for the diagnosis of hepatocellular carcinoma: A large-scale, multicentre study. Lancet Oncol. 2012, 13, 817-826. [CrossRef]
170. Wei, W.; Chua, M.S.; Grepper, S.; So, S.K. Soluble Frizzled-7 receptor inhibits Wnt signaling and sensitizes hepatocellular carcinoma cells towards doxorubicin. Mol. Cancer 2011. [CrossRef] [PubMed]
171. Song, J.; Gao, L.; Yang, G.; Tang, S.; Xie, H.; Wang, Y.; Wang, J.; Zhang, Y.; Jin, J.; Gou, Y. et al. MiR-199a regulates cell proliferation and survival by targeting FZD7. PLoS ONE 2014, 9, e110074. [CrossRef] [PubMed]
172. Burke, Z.D.; Reed, K.R.; Phesse, T.J.; Sansom, O.J.; Clarke, A.R.; Tosh, D. Liver zonation occurs through a beta-catenin-dependent, c-Myc-independent mechanism. Gastroenterology 2009, 136, 2316-2324. [CrossRef] [PubMed]
173. Cadoret, A.; Ovejero, C.; Saadi-Kheddouci, S.; Souil, E.; Fabre, M.; Romagnolo, B.; Kahn, A.; Perret, C. Hepatomegaly in transgenic mice expressing an oncogenic form of beta-catenin. Cancer Res. 2001, 61, 3245-3249. [PubMed]
174. TCGA. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014, 513, 202-209.
175. Wang, K.; Yuen, S.T.; Xu, J.; Lee, S.P.; Yan, H.H.; Shi, S.T.; Siu, H.C.; Deng, S.; Chu, K.M.; Law, S. et al. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat. Genet. 2014, 46, 573-582. [CrossRef] [PubMed]
176. Radulescu, S.; Ridgway, R.A.; Cordero, J.; Athineos, D.; Salgueiro, P.; Poulsom, R.; Neumann, J.; Jung, A.; Patel, S.; Woodgett, J. et al. Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation. Oncogene 2013, 32, 2048-2057. [CrossRef] [PubMed]
177. Nojima, M.; Suzuki, H.; Toyota, M.; Watanabe, Y.; Maruyama, R.; Sasaki, S.; Sasaki, Y.; Mita, H.; Nishikawa, N.; Yamaguchi, K. et al. Frequent epigenetic inactivation of SFRP genes and constitutive activation of Wnt signaling in gastric cancer. Oncogene 2007, 26, 4699-4713. [CrossRef] [PubMed]
178. Wang, W.; Zhao, L.; Ma, Q.; Wang, Q.; Chu, P.K.; Zhang, Y. The role of the Wnt/beta-catenin pathway in the effect of implant topography on MG63 differentiation. Biomaterials 2012, 33, 7993-8002. [CrossRef] [PubMed]
179. Asad, M.; Wong, M.K.; Tan, T.Z.; Choolani, M.; Low, J.; Mori, S.; Virshup, D.; Thiery, J.P.; Huang, R.Y. FZD7 drives in vitro aggressiveness in Stem-A subtype of ovarian cancer via regulation of non-canonical Wnt/PCP pathway. Cell Death Dis. 2014. [CrossRef] [PubMed]
180. Kakiuchi, M.; Nishizawa, T.; Ueda, H.; Gotoh, K.; Tanaka, A.; Hayashi, A.; Yamamoto, S.; Tatsuno, K.; Katoh, H.; Watanabe, Y. et al. Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma. Nat. Genet. 2014, 46, 583-587. [CrossRef] [PubMed]
181. Fukuda, T.; Chen, L.; Endo, T.; Tang, L.; Lu, D.; Castro, J.E.; Widhopf, G.F.; Rassenti, L.Z.; Cantwell, M.J.; Prussak, C.E. et al. Antisera induced by infusions of autologous Ad-CD154-leukemia B cells identify ROR1 as an oncofetal antigen and receptor for Wnt5a. Proc. Natl. Acad. Sci. USA 2008, 105, 3047-3052. [CrossRef] [PubMed]
182. Saitoh, T.; Mine, T.; Katoh, M. Frequent up-regulation of WNT5A mRNA in primary gastric cancer. Int. J. Mol. Med. 2002, 9, 515-519. [CrossRef] [PubMed]
183. Smith, K.; Bui, T.D.; Poulsom, R.; Kaklamanis, L.; Williams, G.; Harris, A.L. Up-regulation of macrophage wnt gene expression in adenoma-carcinoma progression of human colorectal cancer. Br. J. Cancer 1999, 81, 496-502. [CrossRef] [PubMed]
184. Kirikoshi, H.; Sekihara, H.; Katoh, M. Up-regulation of Frizzled-7 (FZD7) in human gastric cancer. Int. J. Oncol. 2001, 19, 111-115. [CrossRef] [PubMed]
185. To, K.F.; Chan, M.W.; Leung, W.K.; Yu, J.; Tong, J.H.; Lee, T.L.; Chan, F.K.; Sung, J.J. Alterations of frizzled (FzE3) and secreted frizzled related protein (hsFRP) expression in gastric cancer. Life Sci. 2001, 70, 483-489. [CrossRef]
186. Schmuck, R.; Warneke, V.; Behrens, H.M.; Simon, E.; Weichert, W.; Rocken, C. Genotypic and phenotypic characterization of side population of gastric cancer cell lines. Am. J. Pathol. 2011, 178, 1792-1804. [CrossRef] [PubMed]
187. Geng, Y.; Lu, X.; Wu, X.; Xue, L.; Wang, X.; Xu, J. MicroRNA-27b suppresses Helicobacter pylori-induced gastric tumorigenesis through negatively regulating Frizzled7. Oncol Rep. 2016, 35, 2441-2450. [CrossRef] [PubMed]
188. Zeng, Y.A.; Nusse, R. Wnt proteins are self-renewal factors for mammary stem cells and promote their long-term expansion in culture. Cell Stem Cell 2010, 6, 568-577. [CrossRef] [PubMed]
189. Veeck, J.; Niederacher, D.; An, H.; Klopocki, E.; Wiesmann, F.; Betz, B.; Galm, O.; Camara, O.; Durst, M.; Kristiansen, G. et al. Aberrant methylation of the Wnt antagonist SFRP1 in breast cancer is associated with unfavourable prognosis. Oncogene 2006, 25, 3479-3488. [CrossRef] [PubMed]
190. Ai, L.; Tao, Q.; Zhong, S.; Fields, C.R.; Kim, W.J.; Lee, M.W.; Cui, Y.; Brown, K.D.; Robertson, K.D. Inactivation of Wnt inhibitory factor-1 (WIF1) expression by epigenetic silencing is a common event in breast cancer. Carcinogenesis 2006, 27, 1341-1348. [CrossRef] [PubMed]
191. Liu, C.C.; Prior, J.; Piwnica-Worms, D.; Bu, G. LRP6 overexpression defines a class of breast cancer subtype and is a target for therapy. Proc. Natl. Acad. Sci. USA 2010, 107, 5136-5141. [CrossRef] [PubMed]
192. Yang, L.; Wu, X.; Wang, Y.; Zhang, K.; Wu, J.; Yuan, Y.C.; Deng, X.; Chen, L.; Kim, C.C.; Lau, S. et al. FZD7 has a critical role in cell proliferation in triple negative breast cancer. Oncogene 2011, 30, 4437-4446. [CrossRef] [PubMed]
193. Simmons, G.E., Jr.; Pandey, S.; Nedeljkovic-Kurepa, A.; Saxena, M.; Wang, A.; Pruitt, K. Frizzled 7 expression is positively regulated by SIRT1 and beta-catenin in breast cancer cells. PLoS ONE 2014, 9, e98861. [CrossRef] [PubMed]
194. Chakrabarti, R.; Wei, Y.; Hwang, J.; Hang, X.; Andres Blanco, M.; Choudhury, A.; Tiede, B.; Romano, R.A.; DeCoste, C.; Mercatali, L. et al. DeltaNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling. Nat. Cell Biol. 2014. [CrossRef] [PubMed]
195. Su, H.Y.; Lai, H.C.; Lin, Y.W.; Chou, Y.C.; Liu, C.Y.; Yu, M.H. An epigenetic marker panel for screening and prognostic prediction of ovarian cancer. Int. J. Cancer 2009, 124, 387-393. [CrossRef] [PubMed]
196. Su, H.Y.; Lai, H.C.; Lin, Y.W.; Liu, C.Y.; Chen, C.K.; Chou, Y.C.; Lin, S.P.; Lin, W.C.; Lee, H.Y.; Yu, M.H. Epigenetic silencing of SFRP5 is related to malignant phenotype and chemoresistance of ovarian cancer through Wnt signaling pathway. Int. J. Cancer 2010, 127, 555-567. [CrossRef] [PubMed]
197. Matei, D.; Graeber, T.G.; Baldwin, R.L.; Karlan, B.Y.; Rao, J.; Chang, D.D. Gene expression in epithelial ovarian carcinoma. Oncogene 2002, 21, 6289-6298. [CrossRef] [PubMed]
198. Shinohara, A.; Yokoyama, Y.; Wan, X.; Takahashi, Y.; Mori, Y.; Takami, T.; Shimokawa, K.; Tamaya, T. Cytoplasmic/nuclear expression without mutation of exon 3 of the beta-catenin gene is frequent in the development of the neoplasm of the uterine cervix. Gynecol. Oncol. 2001, 82, 450-455. [CrossRef] [PubMed]
199. Lee, E.J.; Jo, M.; Rho, S.B.; Park, K.; Yoo, Y.N.; Park, J.; Chae, M.; Zhang, W.; Lee, J.H. Dkk3, downregulated in cervical cancer, functions as a negative regulator of beta-catenin. Int. J. Cancer 2009, 124, 287-297. [CrossRef] [PubMed]
200. Ramachandran, I.; Thavathiru, E.; Ramalingam, S.; Natarajan, G.; Mills, W.K.; Benbrook, D.M.; Zuna, R.; Lightfoot, S.; Reis, A.; Anant, S. et al. Wnt inhibitory factor 1 induces apoptosis and inhibits cervical cancer growth, invasion and angiogenesis in vivo. Oncogene 2012, 31, 2725-2737. [CrossRef] [PubMed]
201. Chung, M.T.; Sytwu, H.K.; Yan, M.D.; Shih, Y.L.; Chang, C.C.; Yu, M.H.; Chu, T.Y.; Lai, H.C.; Lin, Y.W. Promoter methylation of SFRPs gene family in cervical cancer. Gynecol. Oncol. 2009, 112, 301-306. [CrossRef] [PubMed]
202. Deng, B.; Zhang, S.; Miao, Y.; Zhang, Y.; Wen, F.; Guo, K. Down-regulation of Frizzled-7 expression inhibits migration, invasion, and epithelial-mesenchymal transition of cervical cancer cell lines. Med. Oncol. 2015. [CrossRef] [PubMed]
203. Deng, B.; Zhang, Y.; Zhang, S.; Wen, F.; Miao, Y.; Guo, K. MicroRNA-142-3p inhibits cell proliferation and invasion of cervical cancer cells by targeting FZD7. Tumour Biol. 2015, 36, 8065-8073. [CrossRef] [PubMed]
204. Chien, A.J.; Moore, E.C.; Lonsdorf, A.S.; Kulikauskas, R.M.; Rothberg, B.G.; Berger, A.J.; Major, M.B.; Hwang, S.T.; Rimm, D.L.; Moon, R.T. Activated Wnt/beta-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model. Proc. Natl. Acad. Sci. USA 2009, 106, 1193-1198. [CrossRef] [PubMed]
205. Biechele, T.L.; Camp, N.D.; Fass, D.M.; Kulikauskas, R.M.; Robin, N.C.; White, B.D.; Taraska, C.M.; Moore, E.C.; Muster, J.; Karmacharya, R. et al. Chemical-genetic screen identifies riluzole as an enhancer of Wnt/beta-catenin signaling in melanoma. Chem. Biol. 2010, 17, 1177-1182. [CrossRef] [PubMed]
206. Atkinson, J.M.; Rank, K.B.; Zeng, Y.; Capen, A.; Yadav, V.; Manro, J.R.; Engler, T.A.; Chedid, M. Activating the Wnt/beta-Catenin Pathway for the Treatment of Melanoma--Application of LY2090314, a Novel Selective Inhibitor of Glycogen Synthase Kinase-3. PLoS ONE 2015, 10, e0125028. [CrossRef] [PubMed]
207. Spranger, S.; Bao, R.; Gajewski, T.F. Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity. Nature 2015, 523, 231-235. [CrossRef] [PubMed]
208. Anastas, J.N.; Kulikauskas, R.M.; Tamir, T.; Rizos, H.; Long, G.V.; von Euw, E.M.; Yang, P.T.; Chen, H.W.; Haydu, L.; Toroni, R.A. et al. WNT5A enhances resistance of melanoma cells to targeted BRAF inhibitors. J. Clin. Invest. 2014, 124, 2877-2890. [CrossRef] [PubMed]
209. Clarke, T.K.; Dempster, E.; Docherty, S.J.; Desrivieres, S.; Lourdsamy, A.; Wodarz, N.; Ridinger, M.; Maier, W.; Rietschel, M.; Schumann, G. Multiple polymorphisms in genes of the adrenergic stress system confer vulnerability to alcohol abuse. Addict. Biol. 2012, 17, 202-208. [CrossRef] [PubMed]
210. Tiwary, S.; Xu, L. FRIZZLED7 is required for tumor inititation and metastatic growth of melanoma cells. PLoS ONE 2016, 11, e0147638. [CrossRef] [PubMed]
211. Koesters, R.; Ridder, R.; Kopp-Schneider, A.; Betts, D.; Adams, V.; Niggli, F.; Briner, J.; von Knebel Doeberitz, M. Mutational activation of the beta-catenin proto-oncogene is a common event in the development ofWilms' tumors. Cancer Res. 1999, 59, 3880-3882. [PubMed]
212. Dekel, B.; Metsuyanim, S.; Schmidt-Ott, K.M.; Fridman, E.; Jacob-Hirsch, J.; Simon, A.; Pinthus, J.; Mor, Y.; Barasch, J.; Amariglio, N. et al. Multiple imprinted and stemness genes provide a link between normal and tumor progenitor cells of the developing human kidney. Cancer Res. 2006, 66, 6040-6049. [CrossRef] [PubMed]
213. Pode-Shakked, N.; Harari-Steinberg, O.; Haberman-Ziv, Y.; Rom-Gross, E.; Bahar, S.; Omer, D.; Metsuyanim, S.; Buzhor, E.; Jacob-Hirsch, J.; Goldstein, R.S. et al. Resistance or sensitivity of Wilms’ tumor to anti-FZD7 antibody highlights the Wnt pathway as a possible therapeutic target. Oncogene 2011, 30, 1664-1680. [CrossRef] [PubMed]
214. Pecina-Slaus, N.; Pavelic, K.; Pavelic, J. Loss of heterozygosity and protein expression of APC gene in renal cell carcinomas. J. Mol. Med. 1999, 77, 446-453. [CrossRef] [PubMed]
215. Zang, T.; Zhuang, L.; Zhang, Z.; Xin, D.; Guo, Y. Expression of beta-catenin in renal cell carcinoma. Chin. Med. J. 2001, 114, 152-154. [PubMed]
216. Sansom, O.J.; Griffiths, D.F.; Reed, K.R.; Winton, D.J.; Clarke, A.R. Apc deficiency predisposes to renal carcinoma in the mouse. Oncogene 2005, 24, 8205-8210. [CrossRef] [PubMed]
217. Kawamoto, K.; Hirata, H.; Kikuno, N.; Tanaka, Y.; Nakagawa, M.; Dahiya, R. DNA methylation and histone modifications cause silencing of Wnt antagonist gene in human renal cell carcinoma cell lines. Int. J. Cancer 2008, 123, 535-542. [CrossRef] [PubMed]
218. Xu, R.; Zeng, S.; Xie, W.; Sun, C.; Chen, Y.L.; Chen, M.J.; Zhang, L. The expression and function of Frizzled-7 in human renal cell carcinoma. Clin. Transl. Oncol. 2016, 18, 269-276. [CrossRef] [PubMed]
219. Zeng, Z.Y.; Zhou, Y.H.; Zhang, W.L.; Xiong, W.; Fan, S.Q.; Li, X.L.; Luo, X.M.; Wu, M.H.; Yang, Y.X.; Huang, C. et al. Gene expression profiling of nasopharyngeal carcinoma reveals the abnormally regulated Wnt signaling pathway. Hum. Pathol. 2007, 38, 120-133. [CrossRef] [PubMed]
220. Frierson, H.F., Jr.; El-Naggar, A.K.; Welsh, J.B.; Sapinoso, L.M.; Su, A.I.; Cheng, J.; Saku, T.; Moskaluk, C.A.; Hampton, G.M. Large scale molecular analysis identifies genes with altered expression in salivary adenoid cystic carcinoma. Am. J. Pathol. 2002, 161, 1315-1323. [CrossRef]
221. Rhee, C.S.; Sen, M.; Lu, D.; Wu, C.; Leoni, L.; Rubin, J.; Corr, M.; Carson, D.A. Wnt and frizzled receptors as potential targets for immunotherapy in head and neck squamous cell carcinomas. Oncogene 2002, 21, 6598-6605. [CrossRef] [PubMed]
222. Ding, L.; Getz, G.; Wheeler, D.A.; Mardis, E.R.; McLellan, M.D.; Cibulskis, K.; Sougnez, C.; Greulich, H.; Muzny, D.M.; Morgan, M.B. et al. Somatic mutations affect key pathways in lung adenocarcinoma. Nature 2008, 455, 1069-1075. [CrossRef] [PubMed]
223. Nakashima, T.; Liu, D.; Nakano, J.; Ishikawa, S.; Yokomise, H.; Ueno, M.; Kadota, K.; Huang, C.L. Wnt1 overexpression associated with tumor proliferation and a poor prognosis in non-small cell lung cancer patients. Oncol Rep. 2008, 19, 203-209. [CrossRef] [PubMed]
224. Yardy, G.W.; Brewster, S.F. Wnt signalling and prostate cancer. Prostate Cancer Prostatic Dis. 2005, 8, 119-126. [CrossRef] [PubMed]
225. Pearson, H.B.; Phesse, T.J.; Clarke, A.R. K-ras and Wnt signaling synergize to accelerate prostate tumorigenesis in the mouse. Cancer Res. 2009, 69, 94-101. [CrossRef] [PubMed]
226. Balciunaite, G.; Keller, M.P.; Balciunaite, E.; Piali, L.; Zuklys, S.; Mathieu, Y.D.; Gill, J.; Boyd, R.; Sussman, D.J.; Hollander, G.A. Wnt glycoproteins regulate the expression of FoxN1, the gene defective in nude mice. Nat. Immunol. 2002, 3, 1102-1108. [CrossRef] [PubMed]
227. Sandberg, C.J.; Altschuler, G.; Jeong, J.; Stromme, K.K.; Stangeland, B.; Murrell, W.; Grasmo-Wendler, U.H.; Myklebost, O.; Helseth, E.; Vik-Mo, E.O. et al. Comparison of glioma stem cells to neural stem cells from the adult human brain identifies dysregulated Wnt-signaling and a fingerprint associated with clinical outcome. Exp. Cell Res. 2013, 319, 2230-2243. [CrossRef] [PubMed]
228. Kierulf-Vieira, K.S.; Sandberg, C.J.; Grieg, Z.; Gunther, C.C.; Langmoen, I.A.; Vik-Mo, E.O. Wnt inhibition is dysregulated in gliomas and its re-establishment inhibits proliferation and tumor sphere formation. Exp. Cell Res. 2016, 340, 53-61. [CrossRef] [PubMed]
229. Phesse, T.J.; Buchert, M.; Stuart, E.; Flanagan, D.J.; Faux, M.; Afshar-Sterle, S.; Walker, F.; Zhang, H.H.; Nowell, C.J.; Jorissen, R. et al. Partial inhibition of gp130-Jak-Stat3 signaling prevents Wnt-beta-catenin-mediated intestinal tumor growth and regeneration. Sci. Signal. 2014. [CrossRef] [PubMed]
230. Sansom, O.J.; Meniel, V.; Wilkins, J.A.; Cole, A.M.; Oien, K.A.; Marsh, V.; Jamieson, T.J.; Guerra, C.; Ashton, G.H.; Barbacid, M. et al. Loss of Apc allows phenotypic manifestation of the transforming properties of an endogenous K-ras oncogene in vivo. Proc. Natl. Acad. Sci. USA 2006, 103, 14122-14127. [CrossRef] [PubMed]
231. Faller, W.J.; Jackson, T.J.; Knight, J.R.; Ridgway, R.A.; Jamieson, T.; Karim, S.A.; Jones, C.; Radulescu, S.; Huels, D.J.; Myant, K.B. et al. mTORC1-mediated translational elongation limits intestinal tumour initiation and growth. Nature 2015, 517, 497-500. [CrossRef] [PubMed]
232. van Es, J.H.; van Gijn, M.E.; Riccio, O.; van den Born, M.; Vooijs, M.; Begthel, H.; Cozijnsen, M.; Robine, S.; Winton, D.J.; Radtke, F. et al. Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature 2005, 435, 959-963. [CrossRef] [PubMed]
233. Phesse, T.J.; Clarke, A.R. Normal stem cells in cancer prone epithelial tissues. Br. J. Cancer 2009, 100, 221-227. [CrossRef] [PubMed]
234. Visvader, J.E. Cells of origin in cancer. Nature 2011, 469, 314-322. [CrossRef] [PubMed]
235. Brabletz, T.; Jung, A.; Spaderna, S.; Hlubek, F.; Kirchner, T. Opinion: Migrating cancer stem cells--An integrated concept of malignant tumour progression. Nat. Rev. Cancer 2005, 5, 744-749. [CrossRef] [PubMed]
236. Gurney, A.; Axelrod, F.; Bond, C.J.; Cain, J.; Chartier, C.; Donigan, L.; Fischer, M.; Chaudhari, A.; Ji, M.; Kapoun, A.M. et al. Wnt pathway inhibition via the targeting of Frizzled receptors results in decreased growth and tumorigenicity of human tumors. Proc. Natl. Acad. Sci. USA 2012, 109, 11717-11722. [CrossRef] [PubMed]
237. Tai, D.; Wells, K.; Arcaroli, J.; Vanderbilt, C.; Aisner, D.L.; Messersmith, W.A.; Lieu, C.H. Targeting the Wnt signaling pathway in cancer therapeutics. Oncologist 2015, 20, 1189-1198. [CrossRef] [PubMed]