Notch and Wnt signaling pathway in cancer: Crucial role and potential therapeutic targets (Review)

International Journal of Oncology

Volumn 48, Issue 2, 2016, Pages 437-449

  Xiao, Yu Feng ^a   Yong, Xin ^a   Tang, Bo ^a   Qin, Yong ^a   Zhang, Jian Wei ^a   Zhang, Dan ^a   Xie, Rui ^a   Yang, Shi Ming ^a  

^a THIRD MILITARY MEDICAL UNIVERSITY   (China)

Author keywords

Cancer; Notch; Signaling pathway; Therapy; Wnt

Indexed keywords

BETA CATENIN; GAMMA SECRETASE; MONOCLONAL ANTIBODY; NOTCH RECEPTOR; WNT PROTEIN; ANTINEOPLASTIC AGENT;

ARTICLE; BREAST CANCER; COLORECTAL CANCER; ENZYME INHIBITION; ESOPHAGEAL SQUAMOUS CELL CARCINOMA; HEMATOLOGIC MALIGNANCY; LIVER CELL CARCINOMA; LUNG CANCER; MOLECULARLY TARGETED THERAPY; NEOPLASM; NOTCH SIGNALING PATHWAY; PRIORITY JOURNAL; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; STOMACH CANCER; WNT SIGNALING PATHWAY; ANIMAL; DRUG EFFECTS; HUMAN; METABOLISM; NEOPLASMS; PHYSIOLOGY;

ANIMALS; ANTINEOPLASTIC AGENTS; HUMANS; NEOPLASMS; RECEPTORS, NOTCH; WNT SIGNALING PATHWAY;

EID: 84956947667     PISSN: 10196439     EISSN: 17912423     Source Type: Journal    
DOI: 10.3892/ijo.2015.3280     Document Type: Article

References (172)

1. Ramdass B, Duggal R, Minev B, Chowdhary A and Ramdass B, Duggal R, Minev B, Chowdhary A and Koka P: Functional role of solid tumor stem cells in disease etiology and susceptibility to therapeutic interventions. J Stem Cells 8: 189-231, 2013.
2. Chung E and Kondo M: Role of Ras/Raf/MEK/ERK signaling in physiological hematopoiesis and leukemia development. Immunol Res 49: 248-268, 2011.
3. Knight T and Irving JA: Ras/Raf/MEK/ERK pathway activation in childhood acute lymphoblastic leukemia and its therapeutic targeting. Front Oncol 4: 160, 2014.
4. Monga SP: Role and regulation of β-catenin signaling during physiological liver growth. Gene Expr 16: 51-62, 2014.
5. Andersson ER and Lendahl U: Therapeutic modulation of Notch signalling: are we there yet? Nat Rev Drug Discov 13: 357-378, 2014.
6. Pasillas MP, Shields S, Reilly R, Strnadel J, Behl C, Park R, Yates JR III, Klemke R, Gonias SL and Coppinger JA: Proteomic analysis reveals a role for Bcl2-associated athanogene 3 and major vault protein in resistance to apoptosis in senescent cells by regulating ERK1/2 activation. Mol Cell Proteomics 14: 1-14, 2015.
7. Shi X, Wu S, Yang Y, Tang L, Wang Y, Dong J, Lu B, Jiang G and Zhao W: AQP5 silencing suppresses p38 MAPK signaling and improves drug resistance in colon cancer cells. Tumour Biol 35: 7035-7045, 2014.
8. Yu SL, Lee DC, Son JW, Park CG, Lee HY and Kang J: Histone deacetylase 4 mediates SMAD family member 4 deacetylation and induces 5-fluorouracil resistance in breast cancer cells. Oncol Rep 30: 1293-1300, 2013.
9. Jiang AG, Yu H and Huang JA: Expression and clinical significance of the phosphatidylinositol 3-kinase/protein kinase B signal transduction pathway in non-small cell lung carcinoma. Oncol Lett 8: 601-607, 2014.
10. Ogawa R, Ishiguro H, Kimura M, Funahashi H, Wakasugi T, Ando T, Shiozaki M and Takeyama H: NOTCH1 expression predicts patient prognosis in esophageal squamous cell cancer. Eur Surg Ress 51: 101-107, 2013.
11. Chu W, Song X, Yang X, Ma L, Zhu J, He M, Wang Z and Wu Y: Neuropilin-1 promotes epithelial-to-mesenchymal transition by stimulating nuclear factor-kappa B and is associated with poor prognosis in human oral squamous cell carcinoma. PLoS One 9: e101931, 2014.
12. Yao L, Sun B, Zhao X, Zhao X, Gu Q, Dong X, Zheng Y, Sun J, Cheng R, Qi H, et al: Overexpression of Wnt5a promotes angiogenesis in NSCLC. BioMed Res Int 2014: 832562, 2014.
13. Carvalho FL, Simons BW, Eberhart CG and Berman DM: Notch signaling in prostate cancer: A moving target. Prostate 74: 933-945, 2014.
14. Jamieson C, Sharma M and Henderson BR: Targeting the β-catenin nuclear transport pathway in cancer. Semin Cancer Biol 27: 20-29, 2014.
15. Gasparini C, Celeghini C, Monasta L and Zauli G: NF-kappaB pathways in hematological malignancies. Cellular and molecular life sciences. Cell Mol Life Sci 71: 2083-2102, 2014.
16. Tournier C: The 2 Faces of JNK Signaling in Cancer. Genes Cancer 4: 397-400, 2013.
17. Ntziachristos P, Lim JS, Sage J and Aifantis I: From fly wings to targeted cancer therapies: A centennial for notch signaling. Cancer Cell 25: 318-334, 2014.
18. Okajima T and Irvine KD: Regulation of notch signaling by o-linked fucose. Cell 111: 893-904, 2002.
19. Haines N and Irvine KD: Glycosylation regulates Notch signalling. Nat Rev Mol Cell Biol 4: 786-797, 2003.
20. Guo S, Liu M and Gonzalez-Perez RR: Role of Notch and its oncogenic signaling crosstalk in breast cancer. Biochim Biophys Acta 1815: 197-213, 2011.
21. Lai EC: Notch signaling: Control of cell communication and cell fate. Development 131: 965-973, 2004.
22. Wang Z, Li Y, Ahmad A, Azmi AS, Banerjee S, Kong D and Sarkar FH: Targeting Notch signaling pathway to overcome drug resistance for cancer therapy. Biochim Biophys Acta 1806: 258-267, 2010.
23. Kopan R and Ilagan MX: The canonical Notch signaling pathway: Unfolding the activation mechanism. Cell 137: 216-233, 2009.
24. Louvi A and Artavanis-Tsakonas S: Notch and disease: A growing field. Semin Cell Dev Biol 23: 473-480, 2012.
25. Rizzo P, Osipo C, Foreman K, Golde T, Osborne B and Miele L: Rational targeting of Notch signaling in cancer. Oncogene 27: 5124-5131, 2008.
26. Wang Z, Banerjee S, Li Y, Rahman KM, Zhang Y and Sarkar FH: Down-regulation of notch-1 inhibits invasion by inactivation of nuclear factor-kappaB, vascular endothelial growth factor, and matrix metalloproteinase-9 in pancreatic cancer cells. Cancer Res 66: 2778-2784, 2006.
27. Wang Z, Zhang Y, Li Y, Banerjee S, Liao J and Sarkar FH: Down-regulation of Notch-1 contributes to cell growth inhibition and apoptosis in pancreatic cancer cells. Mol Cancer Ther 5: 483-493, 2006.
28. Zavadil J, Cermak L, Soto-Nieves N and Bottinger EP: Integration of TGF-beta/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition. EMBO J 23: 1155-1165, 2004.
29. Sansone P, Storci G, Tavolari S, Guarnieri T, Giovannini C, Taffurelli M, Ceccarelli C, Santini D, Paterini P, Marcu KB, et al: IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. J Clin Invest 117: 3988-4002, 2007.
30. Patel NS, Li JL, Generali D, Poulsom R, Cranston DW and Harris AL: Up-regulation of delta-like 4 ligand in human tumor vasculature and the role of basal expression in endothelial cell function. Cancer Res 65: 8690-8697, 2005.
31. Lawson ND, Vogel AM and Weinstein BM: sonic hedgehog and vascular endothelial growth factor act upstream of the Notch pathway during arterial endothelial differentiation. Dev Cell 3: 127-136, 2002.
32. South AP, Cho RJ and Aster JC: The double-edged sword of Notch signaling in cancer. Semin Cell Dev Biol 23: 458-464, 2012.
33. Ellisen LW, Bird J, West DC, Soreng AL, Reynolds TC, Smith SD and Sklar J: TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell 66: 649-661, 1991.
34. Capobianco AJ, Zagouras P, Blaumueller CM, Artavanis-Tsakonas S and Bishop JM: Neoplastic transformation by truncated alleles of human NOTCH1/TAN1 and NOTCH2. Mol Cell Biol 17: 6265-6273, 1997.
35. Girard L, Hanna Z, Beaulieu N, Hoemann CD, Simard C, Kozak CA and Jolicoeur P: Frequent provirus insertional mutagenesis of Notch1 in thymomas of MMTVD/myc transgenic mice suggests a collaboration of c-myc and Notch1 for oncogenesis. Genes Dev 10: 1930-1944, 1996.
36. Weng AP, Ferrando AA, Lee W, Morris JP IV, Silverman LB, Sanchez-Irizarry C, Blacklow SC, Look AT and Aster JC: Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 306: 269-271, 2004.
37. Radtke F, Wilson A, Mancini SJ and MacDonald HR: Notch regulation of lymphocyte development and function. Nat Immunol 5: 247-253, 2004.
38. Hoyne GF: Notch signaling in the immune system. J Leukoc Biol 74: 971-981, 2003.
39. Sulis ML, Williams O, Palomero T, Tosello V, Pallikuppam S, Real PJ, Barnes K, Zuurbier L, Meijerink JP and Ferrando AA: NOTCH1 extracellular juxtamembrane expansion mutations in T-ALL. Blood 112: 733-740, 2008.
40. Breit S, Stanulla M, Flohr T, Schrappe M, Ludwig WD, Tolle G, Happich M, Muckenthaler MU and Kulozik AE: Activating NOTCH1 mutations predict favorable early treatment response and long-term outcome in childhood precursor T-cell lymphoblastic leukemia. Blood 108: 1151-1157, 2006.
41. Park MJ, Taki T, Oda M, Watanabe T, Yumura-Yagi K, Kobayashi R, Suzuki N, Hara J, Horibe K and Hayashi Y: FBXW7 and NOTCH1 mutations in childhood T cell acute lymphoblastic leukaemia and T cell non-Hodgkin lymphoma. Br J Haematol 145: 198-206, 2009.
42. Clappier E, Collette S, Grardel N, Girard S, Suarez L, Brunie G, Kaltenbach S, Yakouben K, Mazingue F, Robert A, et al; EORTC-CLG: NOTCH1 and FBXW7 mutations have a favorable impact on early response to treatment, but not on outcome, in children with T-cell acute lymphoblastic leukemia (T-ALL) treated on EORTC trials 58881 and 58951. Leukemia 24: 2023-2031, 2010.
43. Weissmann S, Roller A, Jeromin S, Hernandez M, Abaigar M, Hernandez-Rivas JM, Grossmann V, Haferlach C, Kern W, Haferlach T, et al: Prognostic impact and landscape of NOTCH1 mutations in chronic lymphocytic leukemia (CLL): A study on 852 patients. Leukemia 27: 2393-2396, 2013.
44. Di Ianni M, Baldoni S, Rosati E, Ciurnelli R, Cavalli L, Martelli MF, Marconi P, Screpanti I and Falzetti F: A new genetic lesion in B-CLL: A NOTCH1 PEST domain mutation. Br J Haematol 146: 689-691, 2009.
45. Sportoletti P, Baldoni S, Cavalli L, Del Papa B, Bonifacio E, Ciurnelli R, Bell AS, Di Tommaso A, Rosati E, Crescenzi B, et al: NOTCH1 PEST domain mutation is an adverse prognostic factor in B-CLL. Br J Haematol 151: 404-406, 2010.
46. Wickremasinghe RG, Prentice AG and Steele AJ: p53 and Notch signaling in chronic lymphocytic leukemia: Clues to identifying novel therapeutic strategies. Leukemia 25: 1400-1407, 2011.
47. Rossi D, Rasi S, Fabbri G, Spina V, Fangazio M, Forconi F, Marasca R, Laurenti L, Bruscaggin A, Cerri M, et al: Mutations of NOTCH1 are an independent predictor of survival in chronic lymphocytic leukemia. Blood 119: 521-529, 2012.
48. Kiel MJ, Velusamy T, Betz BL, Zhao L, Weigelin HG, Chiang MY, Huebner-Chan DR, Bailey NG, Yang DT, Bhagat G, et al: Whole-genome sequencing identifies recurrent somatic NOTCH2 mutations in splenic marginal zone lymphoma. J Exp Med 209: 1553-1565, 2012.
49. Lee SY, Kumano K, Nakazaki K, Sanada M, Matsumoto A, Yamamoto G, Nannya Y, Suzuki R, Ota S, Ota Y, et al: Gainof-function mutations and copy number increases of Notch2 in diffuse large B-cell lymphoma. Cancer Sci 100: 920-926, 2009.
50. Rossi D, Trifonov V, Fangazio M, Bruscaggin A, Rasi S, Spina V, Monti S, Vaisitti T, Arruga F, Fama R, et al: The coding genome of splenic marginal zone lymphoma: Activation of NOTCH2 and other pathways regulating marginal zone development. J Exp Med 209: 1537-1551, 2012.
51. Uyttendaele H, Soriano JV, Montesano R and Kitajewski J: Notch4 and Wnt-1 proteins function to regulate branching morphogenesis of mammary epithelial cells in an opposing fashion. Dev Biol 196: 204-217, 1998.
52. Bellavia D, Checquolo S, Campese AF, Felli MP, Gulino A and Screpanti I: Notch3: From subtle structural differences to functional diversity. Oncogene 27: 5092-5098, 2008.
53. Melchor L and Smalley MJ: Highway to heaven: Mammary gland development and differentiation. Breast Cancer Res 10: 305, 2008.
54. Weijzen S, Rizzo P, Braid M, Vaishnav R, Jonkheer SM, Zlobin A, Osborne BA, Gottipati S, Aster JC, Hahn WC, et al: Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells. Nat Med 8: 979-986, 2002.
55. Hu C, Dievart A, Lupien M, Calvo E, Tremblay G and Jolicoeur P: Overexpression of activated murine Notch1 and Notch3 in transgenic mice blocks mammary gland development and induces mammary tumors. Am J Pathol 168: 973-990, 2006.
56. Imatani A and Callahan R: Identification of a novel NOTCH-4/ INT-3 RNA species encoding an activated gene product in certain human tumor cell lines. Oncogene 19: 223-231, 2000.
57. Reedijk M, Odorcic S, Chang L, Zhang H, Miller N, McCready DR, Lockwood G and Egan SE: High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival. Cancer Res 65: 8530-8537, 2005.
58. Zhang Z, Wang H, Ikeda S, Fahey F, Bielenberg D, Smits P and Hauschka PV: Notch3 in human breast cancer cell lines regulates osteoblast-cancer cell interactions and osteolytic bone metastasis. Am J Pathol 177: 1459-1469, 2010.
59. Parr C, Watkins G and Jiang WG: The possible correlation of Notch-1 and Notch-2 with clinical outcome and tumour clinicopathological parameters in human breast cancer. Int J Mol Med 14: 779-786, 2004.
60. Baumgart A, Mazur PK, Anton M, Rudelius M, Schwamborn K, Feuchtinger A, Behnke K, Walch A, Braren R, Peschel C, et al: Opposing role of Notch1 and Notch2 in a Kras(G12D)-driven murine non-small cell lung cancer model. Oncogene 34: 578-588, 2015.
61. Yang Y, Yan X, Duan W, Yan J, Yi W, Liang Z, Wang N, Li Y, Chen W, Yu S, et al: Pterostilbene exerts antitumor activity via the Notch1 signaling pathway in human lung adenocarcinoma cells. PLoS One 8: e62652, 2013.
62. Licciulli S, Avila JL, Hanlon L, Troutman S, Cesaroni M, Kota S, Keith B, Simon MC, Pure E, Radtke F, et al: Notch1 is required for Kras-induced lung adenocarcinoma and controls tumor cell survival via p53. Cancer Res 73: 5974-5984, 2013.
63. Xie M, He CS, Wei SH and Zhang L: Notch-1 contributes to epidermal growth factor receptor tyrosine kinase inhibitor acquired resistance in non-small cell lung cancer in vitro and in vivo. Eur J Cancer 49: 3559-3572, 2013.
64. Hassan KA, Wang L, Korkaya H, Chen G, Maillard I, Beer DG, Kalemkerian GP and Wicha M: Notch pathway activity identifies cells with cancer stem cell-like properties and correlates with worse survival in lung adenocarcinoma. Clin Cancer Res 19: 1972-1980, 2013.
65. Theys J, Yahyanejad S, Habets R, Span P, Dubois L, Paesmans K, Kattenbeld B, Cleutjens J, Groot AJ, Schuurbiers OC, et al: High NOTCH activity induces radiation resistance in non small cell lung cancer. Radiother Oncol 108: 440-445, 2013.
66. Wael H, Yoshida R, Kudoh S, Hasegawa K, Niimori-Kita K and Ito T: Notch1 signaling controls cell proliferation, apoptosis and differentiation in lung carcinoma. Lung Cancer 85: 131-140, 2014.
67. Huang J, Song H, Liu B, Yu B, Wang R and Chen L: Expression of Notch-1 and its clinical significance in different histological subtypes of human lung adenocarcinoma. J Exp Clin Cancer Res 32: 84, 2013.
68. Zhou M, Jin WY, Fan ZW and Han RC: Analysis of the expression of the Notch3 receptor protein in adult lung cancer. Oncol Lett 5: 499-504, 2013.
69. Ye YZ, Zhang ZH, Fan XY, Xu XL, Chen ML, Chang BW and Zhang YB: Notch3 overexpression associates with poor prognosis in human non-small-cell lung cancer. Med Oncol 30: 595, 2013.
70. Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin 61: 69-90, 2011.
71. Yeh TS, Wu CW, Hsu KW, Liao WJ, Yang MC, Li AF, Wang AM, Kuo ML and Chi CW: The activated Notch1 signal pathway is associated with gastric cancer progression through cyclooxygenase-2. Cancer Res 69: 5039-5048, 2009.
72. Yao J and Qian C: Over-activated Notch-1 protects gastric carcinoma BGC-823 cells from TNFalpha-induced apoptosis. Dig Liver Dis 41: 867-874, 2009.
73. Carson C, Murdoch B and Roskams AJ: Notch 2 and Notch 1/3 segregate to neuronal and glial lineages of the developing olfactory epithelium. Dev Dyn 235: 1678-1688, 2006.
74. Sun Y, Gao X, Liu J, Kong QY, Wang XW, Chen XY, Wang Q, Cheng YF, Qu XX and Li H: Differential Notch1 and Notch2 expression and frequent activation of Notch signaling in gastric cancers. Arch Pathol Lab Med 135: 451-458, 2011.
75. Tseng YC, Tsai YH, Tseng MJ, Hsu KW, Yang MC, Huang KH, Li AF, Chi CW, Hsieh RH, Ku HH, et al: Notch2-induced COX-2 expression enhancing gastric cancer progression. Mol Carcinog 51: 939-951, 2012.
76. Guo LY, Li YM, Qiao L, Liu T, Du YY, Zhang JQ, He WT, Zhao YX and He DQ: Notch2 regulates matrix metallopeptidase 9 via PI3K/AKT signaling in human gastric carcinoma cell MKN-45. World J Gastroenterol 18: 7262-7270, 2012.
77. Piazzi G, Fini L, Selgrad M, Garcia M, Daoud Y, Wex T, Malfertheiner P, Gasbarrini A, Romano M, Meyer RL, et al: Epigenetic regulation of Delta-Like1 controls Notch1 activation in gastric cancer. Oncotarget 2: 1291-1301, 2011.
78. Pellegrinet L, Rodilla V, Liu Z, Chen S, Koch U, Espinosa L, Kaestner KH, Kopan R, Lewis J and Radtke F: Dll1-and dll4-mediated notch signaling are required for homeostasis of intestinal stem cells. Gastroenterology 140: 1230-1240.e7, 2011.
79. Li GG, Li L, Li C, Ye LY, Li XW, Liu DR, Bao Q, Zheng YX, Xiang DP, Chen L, et al: Influence of up-regulation of Notch ligand DLL4 on biological behaviors of human gastric cancer cells. World J Gastroenterol 19: 4486-4494, 2013.
80. Sun HW, Wu C, Tan HY and Wang QS: Combination DLL4 with Jagged1-siRNA can enhance inhibition of the proliferation and invasiveness activity of human gastric carcinoma by Notch1/ VEGF pathway. Hepatogastroenterology 59: 924-929, 2012.
81. Logan CY and Nusse R: The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20: 781-810, 2004.
82. Rosenbluh J, Wang X and Hahn WC: Genomic insights into WNT/β-catenin signaling. Trends Pharmacol Sci 35: 103-109, 2014.
83. MacDonald BT, Tamai K and He X: Wnt/beta-catenin signaling: Components, mechanisms, and diseases. Dev Cell 17: 9-26, 2009.
84. Niehrs C: The complex world of WNT receptor signalling. Nat Rev Mol Cell Biol 13: 767-779, 2012.
85. Wang JM, Huang FC, Kuo MH, Wang ZF, Tseng TY, Chang LC, Yen SJ, Chang TC and Lin JJ: Inhibition of cancer cell migration and invasion through suppressing the Wnt1-mediating signal pathway by G-quadruplex structure stabilizers. J Biol Chem 289: 14612-14623, 2014.
86. Lee MA, Park JH, Rhyu SY, Oh ST, Kang WK and Kim HN: Wnt3a expression is associated with MMP-9 expression in primary tumor and metastatic site in recurrent or stage IV colorectal cancer. BMC Cancer 14: 125, 2014.
87. Wang SH, Li N, Wei Y, Li QR and Yu ZP: β-catenin deacetylation is essential for WNT-induced proliferation of breast cancer cells. Mol Med Rep 9: 973-978, 2014.
88. Miao CG, Yang YY, He X, Huang C, Huang Y, Zhang L, Lv XW, Jin Y and Li J: Wnt signaling in liver fibrosis: Progress, challenges and potential directions. Biochimie 95: 2326-2335, 2013.
89. Arend RC, Londono-Joshi AI, Straughn JM Jr and Buchsbaum DJ: The Wnt/β-catenin pathway in ovarian cancer: A review. Gynecol Oncol 131: 772-779, 2013.
90. Holland JD, Klaus A, Garratt AN and Birchmeier W: Wnt signaling in stem and cancer stem cells. Curr Opin Cell Biol 25: 254-264, 2013.
91. Barbolina MV, Burkhalter RJ and Stack MS: Diverse mechanisms for activation of Wnt signalling in the ovarian tumour microenvironment. Biochem J 437: 1-12, 2011.
92. Andersen P, Uosaki H, Shenje LT and Kwon C: Non-canonical Notch signaling: Emerging role and mechanism. Trends Cell Biol 22: 257-265, 2012.
93. Clark CE, Nourse CC and Cooper HM: The tangled web of noncanonical Wnt signalling in neural migration. Neurosignals 20: 202-220, 2012.
94. Gonzalez-Sancho JM, Brennan KR, Castelo-Soccio LA and Brown AM: Wnt proteins induce dishevelled phosphorylation via an LRP5/6-independent mechanism, irrespective of their ability to stabilize beta-catenin. Mol Cell Biol 24: 4757-4768, 2004.
95. Beier F and Loeser RF: Biology and pathology of Rho GTPase, PI-3 kinase-Akt, and MAP kinase signaling pathways in chondrocytes. J Cell Biochem 110: 573-580, 2010.
96. Asad M, Wong MK, Tan TZ, Choolani M, Low J, Mori S, Virshup D, Thiery JP and Huang RY: FZD7 drives in vitro aggressiveness in Stem-A subtype of ovarian cancer via regulation of non-canonical Wnt/PCP pathway. Cell Death Dis 5: e1346, 2014.
97. Bernemann C, Hulsewig C, Ruckert C, Schafer S, Blumel L, Hempel G, Gotte M, Greve B, Barth PJ, Kiesel L, et al: Influence of secreted frizzled receptor protein 1 (SFRP1) on neoadjuvant chemotherapy in triple negative breast cancer does not rely on WNT signaling. Mol Cancer 13: 174, 2014.
98. Xi Y and Chen Y: Wnt signaling pathway: Implications for therapy in lung cancer and bone metastasis. Cancer Lett 353: 8-16, 2014.
99. Nejak-Bowen KN and Monga SP: Beta-catenin signaling, liver regeneration and hepatocellular cancer: Sorting the good from the bad. Semin Cancer Biol 21: 44-58, 2011.
100. Colussi D, Brandi G, Bazzoli F and Ricciardiello L: Molecular pathways involved in colorectal cancer: Implications for disease behavior and prevention. Int J Mol Sci 14: 16365-16385, 2013.
101. Pez F, Lopez A, Kim M, Wands JR, Caron de Fromentel C and Merle P: Wnt signaling and hepatocarcinogenesis: Molecular targets for the development of innovative anticancer drugs. J Hepatol 59: 1107-1117, 2013.
102. Armengol C, Cairo S, Fabre M and Buendia MA: Wnt signaling and hepatocarcinogenesis: The hepatoblastoma model. Int J Biochem Cell Biol 43: 265-270, 2011.
103. Gedaly R, Galuppo R, Daily MF, Shah M, Maynard E, Chen C, Zhang X, Esser KA, Cohen DA, Evers BM, et al: Targeting the Wnt/β-catenin signaling pathway in liver cancer stem cells and hepatocellular carcinoma cell lines with FH535. PLoS One 9: e99272, 2014.
104. Hou L, Wang X, Zhou Y, Ma H, Wang Z, He J, Hu H, Guan W and Ma Y: Inhibitory effect and mechanism of mesenchymal stem cells on liver cancer cells. Tumour Biol 35: 1239-1250, 2014.
105. Zucchini-Pascal N, Peyre L and Rahmani R: Crosstalk between beta-catenin and snail in the induction of epithelial to mesenchymal transition in hepatocarcinoma: Role of the ERK1/2 pathway. Int J Mol Sci 14: 20768-20792, 2013.
106. Bustos VH, Ferrarese A, Venerando A, Marin O, Allende JE and Pinna LA: The first armadillo repeat is involved in the recognition and regulation of beta-catenin phosphorylation by protein kinase CK1. Proc Natl Acad Sci USA 103: 19725-19730, 2006.
107. Singh Y, Port J, Schwarz M and Braeuning A: Genetic ablation of β-catenin inhibits the proliferative phenotype of mouse liver adenomas. Br J Cancer 111: 132-138, 2014.
108. Calderaro J, Nault JC, Bioulac-Sage P, Laurent A, Blanc JF, Decaens T and Zucman-Rossi J: ALDH3A1 is overexpressed in a subset of hepatocellular carcinoma characterised by activation of the Wnt/ss-catenin pathway. Virchows Arch 464: 53-60, 2014.
109. Cheng JH, She H, Han YP, Wang J, Xiong S, Asahina K and Tsukamoto H: Wnt antagonism inhibits hepatic stellate cell activation and liver fibrosis. Am J Physiol Gastrointest Liver Physiol 294: G39-G49, 2008.
110. Li W, Zhu C, Li Y, Wu Q and Gao R: Mest attenuates CCl4-induced liver fibrosis in rats by inhibiting the Wnt/β-catenin signaling pathway. Gut Liver 8: 282-291, 2014.
111. Tenesa A and Dunlop MG: New insights into the aetiology of colorectal cancer from genome-wide association studies. Nat Rev Genet 10: 353-358, 2009.
112. Pandurangan AK: Potential targets for prevention of colorectal cancer: A focus on PI3K/Akt/mTOR and Wnt pathways. Asian Pac J Cancer Prev 14: 2201-2205, 2013.
113. Curtin JC: Novel drug discovery opportunities for colorectal cancer. Expert Opin Drug Discov 8: 1153-1164, 2013.
114. Sparks AB, Morin PJ, Vogelstein B and Kinzler KW: Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer. Cancer Res 58: 1130-1134, 1998.
115. Murakami T, Mitomi H, Saito T, Takahashi M, Sakamoto N, Fukui N, Yao T and Watanabe S: Distinct WNT/beta-catenin signaling activation in the serrated neoplasia pathway and the adenoma-carcinoma sequence of the colorectum. Mod Pathol 28: 146-158, 2015.
116. Raghu D and Karunagaran D: Plumbagin downregulates Wnt signaling independent of p53 in human colorectal cancer cells. J Nat Prod 77: 1130-1134, 2014.
117. Tai WP, Hu PJ, Wu J and Lin XC: The inhibition of Wnt/β-catenin signaling pathway in human colon cancer cells by sulindac. Tumori 100: 97-101, 2014.
118. Tumova L, Pombinho AR, Vojtechova M, Stancikova J, Gradl D, Krausova M, Sloncova E, Horazna M, Kriz V, Machonova O, et al: Monensin inhibits canonical Wnt signaling in human colorectal cancer cells and suppresses tumor growth in multiple intestinal neoplasia mice. Mol Cancer Ther 13: 812-822, 2014.
119. Bruun J, Kolberg M, Nesland JM, Svindland A, Nesbakken A and Lothe RA: Prognostic Significance of β-catenin, E-cadherin, and SOX9 in colorectal cancer: Results from a large populationrepresentative series. Front Oncol 4: 118, 2014.
120. Voorham QJ, Janssen J, Tijssen M, Snellenberg S, Mongera S, van Grieken NC, Grabsch H, Kliment M, Rembacken BJ, Mulder CJ, et al: Promoter methylation of Wnt-antagonists in polypoid and nonpolypoid colorectal adenomas. BMC Cancer 13: 603, 2013.
121. Serafino A, Moroni N, Zonfrillo M, Andreola F, Mercuri L, Nicotera G, Nunziata J, Ricci R, Antinori A, Rasi G, et al: WNT-pathway components as predictive markers useful for diagnosis, prevention and therapy in inflammatory bowel disease and sporadic colorectal cancer. Oncotarget 5: 978-992, 2014.
122. Abdelmaksoud-Dammak R, Miladi-Abdennadher I, Saadallah-Kallel A, Khabir A, Sellami-Boudawara T, Frikha M, Daoud J and Mokdad-Gargouri R: Downregulation of WIF-1 and Wnt5a in patients with colorectal carcinoma: clinical significance. Tumour Biol 35: 7975-7982, 2014.
123. Bauer M, Benard J, Gaasterland T, Willert K and Cappellen D: WNT5A encodes two isoforms with distinct functions in cancers. PLoS One 8: e80526, 2013.
124. Chai J, Modak C, Ouyang Y, Wu SY and Jamal MM: CCN1 Induces β-catenin translocation in esophageal squamous cell carcinoma through integrin α11. ISRN Gastroenterol 2012: 207235, 2012.
125. Moyes LH, McEwan H, Radulescu S, Pawlikowski J, Lamm CG, Nixon C, Sansom OJ, Going JJ, Fullarton GM and Adams PD: Activation of Wnt signalling promotes development of dysplasia in Barrett's oesophagus. J Pathol 228: 99-112, 2012.
126. Long A, Giroux V, Whelan KA, Hamilton KE, Tetreault MP, Tanaka K, Lee JS, Klein-Szanto AJ, Nakagawa H and Rustgi AK: WNT10A promotes an invasive and self-renewing phenotype in esophageal squamous cell carcinoma. Carcinogenesis 36: 598-606, 2015.
127. Yang SH, Li SL, Dong ZM and Kan QC: Epigenetic inactivation of Wnt inhibitory factor-1 in human esophageal squamous cell carcinoma. Oncol Res 20: 123-130, 2012.
128. Ge XS, Ma HJ, Zheng XH, Ruan HL, Liao XY, Xue WQ, Chen YB, Zhang Y and Jia WH: HOTAIR, a prognostic factor in esophageal squamous cell carcinoma, inhibits WIF-1 expression and activates Wnt pathway. Cancer Sci 104: 1675-1682, 2013.
129. Liu K, Luo Y, Tian H, Yu KZ, He JX and Shen WY: The tumor suppressor LKB1 antagonizes WNT signaling pathway through modulating GSK3beta activity in cell growth of esophageal carcinoma. Tumour Biol 35: 995-1002, 2014.
130. Tong X, Li L, Li X, Heng L, Zhong L, Su X, Rong R, Hu S, Liu W, Jia B, et al: SOX10, a novel HMG-box-containing tumor suppressor, inhibits growth and metastasis of digestive cancers by suppressing the Wnt/β-catenin pathway. Oncotarget 5: 10571-10583, 2014.
131. Kuramoto T, Goto H, Mitsuhashi A, Tabata S, Ogawa H, Uehara H, Saijo A, Kakiuchi S, Maekawa Y, Yasutomo K, et al: Dll4-Fc, an inhibitor of Dll4-notch signaling, suppresses liver metastasis of small cell lung cancer cells through the downregulation of the NF-κB activity. Mol Cancer Ther 11: 2578-2587, 2012.
132. Stewart KS, Zhou Z, Zweidler-McKay P and Kleinerman ES: Delta-like ligand 4-Notch signaling regulates bone marrowderived pericyte/vascular smooth muscle cell formation. Blood 117: 719-726, 2011.
133. Ridgway J, Zhang G, Wu Y, Stawicki S, Liang WC, Chanthery Y, Kowalski J, Watts RJ, Callahan C, Kasman I, et al: Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis. Nature 444: 1083-1087, 2006.
134. Oishi H, Sunamura M, Egawa S, Motoi F, Unno M, Furukawa T, Habib NA and Yagita H: Blockade of delta-like ligand 4 signaling inhibits both growth and angiogenesis of pancreatic cancer. Pancreas 39: 897-903, 2010.
135. Gurney A and Hoey T: Anti-DLL4, a cancer therapeutic with multiple mechanisms of action. Vasc Cell 3: 18, 2011.
136. Fischer M, Yen WC, Kapoun AM, Wang M, O'Young G, Lewicki J, Gurney A and Hoey T: Anti-DLL4 inhibits growth and reduces tumor-initiating cell frequency in colorectal tumors with oncogenic KRAS mutations. Cancer Res 71: 1520-1525, 2011.
137. Jenkins DW, Ross S, Veldman-Jones M, Foltz IN, Clavette BC, Manchulenko K, Eberlein C, Kendrew J, Petteruti P, Cho S, et al: MEDI0639: A novel therapeutic antibody targeting Dll4 modulates endothelial cell function and angiogenesis in vivo. Mol Cancer Ther 11: 1650-1660, 2012.
138. Liu SK, Bham SA, Fokas E, Beech J, Im J, Cho S, Harris AL and Muschel RJ: Delta-like ligand 4-notch blockade and tumor radiation response. J Natl Cancer Inst 103: 1778-1798, 2011.
139. El Kaffas A, Nofiele J, Giles A, Cho S, Liu SK and Czarnota GJ: Dll4-notch signalling blockade synergizes combined ultrasound-stimulated microbubble and radiation therapy in human colon cancer xenografts. PLoS One 9: e93888, 2014.
140. Aste-Amezaga M, Zhang N, Lineberger JE, Arnold BA, Toner TJ, Gu M, Huang L, Vitelli S, Vo KT, Haytko P, et al: Characterization of Notch1 antibodies that inhibit signaling of both normal and mutated Notch1 receptors. PLoS One 5: e9094, 2010.
141. Sharma A, Paranjape AN, Rangarajan A and Dighe RR: A monoclonal antibody against human Notch1 ligand-binding domain depletes subpopulation of putative breast cancer stem-like cells. Mol Cancer Ther 11: 77-86, 2012.
142. Yan M, Callahan CA, Beyer JC, Allamneni KP, Zhang G, Ridgway JB, Niessen K and Plowman GD: Chronic DLL4 blockade induces vascular neoplasms. Nature 463: E6-E7, 2010.
143. Rosati E, Sabatini R, De Falco F, Del Papa B, Falzetti F, Di Ianni M, Cavalli L, Fettucciari K, Bartoli A, Screpanti I, et al: gamma-Secretase inhibitor I induces apoptosis in chronic lymphocytic leukemia cells by proteasome inhibition, endoplasmic reticulum stress increase and notch down-regulation. Int J Cancer 132: 1940-1953, 2013.
144. Palagani V, El Khatib M, Kossatz U, Bozko P, Muller MR, Manns MP, Krech T, Malek NP and Plentz RR: Epithelial mesenchymal transition and pancreatic tumor initiating CD44+/ EpCAM+ cells are inhibited by γ-secretase inhibitor IX. PLoS One 7: e46514, 2012.
145. Schott AF, Landis MD, Dontu G, Griffith KA, Layman RM, Krop I, Paskett LA, Wong H, Dobrolecki LE, Lewis MT, et al: Preclinical and clinical studies of gamma secretase inhibitors with docetaxel on human breast tumors. Clin Cancer Res 19: 1512-1524, 2013.
146. Lopez-Guerra M, Xargay-Torrent S, Rosich L, Montraveta A, Roldan J, Matas-Cespedes A, Villamor N, Aymerich M, Lopez-Otin C, Perez-Galan P, et al: The γ-secretase inhibitor PF-03084014 combined with fludarabine antagonizes migration, invasion and angiogenesis in NOTCH1-mutated CLL cells. Leukemia 29: 96-106, 2015.
147. Saito N, Fu J, Zheng S, Yao J, Wang S, Liu DD, Yuan Y, Sulman EP, Lang FF, Colman H, et al: A high Notch pathway activation predicts response to γ secretase inhibitors in proneural subtype of glioma tumor-initiating cells. Stem Cells 32: 301-312, 2014.
148. Groeneweg JW, Hall TR, Zhang L, Kim M, Byron VF, Tambouret R, Sathayanrayanan S, Foster R, Rueda BR and Growdon WB: Inhibition of gamma-secretase activity impedes uterine serous carcinoma growth in a human xenograft model. Gynecol Oncol 133: 607-615, 2014.
149. Li LC, Peng Y, Liu YM, Wang LL and Wu XL: Gastric cancer cell growth and epithelial-mesenchymal transition are inhibited by γ-secretase inhibitor DAPT. Oncol Lett 7: 2160-2164, 2014.
150. Dahmani R, Just PA and Perret C: The Wnt/β-catenin pathway as a therapeutic target in human hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 35: 709-713, 2011.
151. Fontenot E, Rossi E, Mumper R, Snyder S, Siamakpour-Reihani S, Ma P, Hilliard E, Bone B, Ketelsen D, Santos C, et al: A novel monoclonal antibody to secreted frizzled-related protein 2 inhibits tumor growth. Mol Cancer Ther 12: 685-695, 2013.
152. Wang Y, Shek FH, Wong KF, Liu LX, Zhang XQ, Yuan Y, Khin E, Hu MY, Wang JH, Poon RT, et al: Anti-cadherin-17 antibody modulates beta-catenin signaling and tumorigenicity of hepatocellular carcinoma. PLoS One 8: e72386, 2013.
153. Gao W, Kim H, Feng M, Phung Y, Xavier CP, Rubin JS and Ho M: Inactivation of Wnt signaling by a human antibody that recognizes the heparan sulfate chains of glypican-3 for liver cancer therapy. Hepatology 60: 576-587, 2014.
154. Ettenberg SA, Charlat O, Daley MP, Liu S, Vincent KJ, Stuart DD, Schuller AG, Yuan J, Ospina B, Green J, et al: Inhibition of tumorigenesis driven by different Wnt proteins requires blockade of distinct ligand-binding regions by LRP6 antibodies. Proc Natl Acad Sci USA 107: 15473-15478, 2010.
155. Gong Y, Bourhis E, Chiu C, Stawicki S, DeAlmeida VI, Liu BY, Phamluong K, Cao TC, Carano RA, Ernst JA, et al: Wnt isoform-specific interactions with coreceptor specify inhibition or potentiation of signaling by LRP6 antibodies. PLoS One 5: e12682, 2010.
156. Lavergne E, Hendaoui I, Coulouarn C, Ribault C, Leseur J, Eliat PA, Mebarki S, Corlu A, Clement B and Musso O: Blocking Wnt signaling by SFRP-like molecules inhibits in vivo cell proliferation and tumor growth in cells carrying active β-catenin. Oncogene 30: 423-433, 2011.
157. Wei W, Chua MS, Grepper S and So SK: Soluble Frizzled-7 receptor inhibits Wnt signaling and sensitizes hepatocellular carcinoma cells towards doxorubicin. Mol Cancer 10: 16, 2011.
158. Amado NG, Predes D, Moreno MM, Carvalho IO, Mendes FA and Abreu JG: Flavonoids and Wnt/β-catenin signaling: Potential role in colorectal cancer therapies. Int J Mol Sci 15: 12094-12106, 2014.
159. Ji Q, Liu X, Fu X, Zhang L, Sui H, Zhou L, Sun J, Cai J, Qin J, Ren J, et al: Resveratrol inhibits invasion and metastasis of colorectal cancer cells via MALAT1 mediated Wnt/β-catenin signal pathway. PLoS One 8: e78700, 2013.
160. Huang SM, Mishina YM, Liu S, Cheung A, Stegmeier F, Michaud GA, Charlat O, Wiellette E, Zhang Y, Wiessner S, et al: Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 461: 614-620, 2009.
161. Waaler J, Machon O, Tumova L, Dinh H, Korinek V, Wilson SR, Paulsen JE, Pedersen NM, Eide TJ, Machonova O, et al: A novel tankyrase inhibitor decreases canonical Wnt signaling in colon carcinoma cells and reduces tumor growth in conditional APC mutant mice. Cancer Res 72: 2822-2832, 2012.
162. Park HY, Toume K, Arai MA, Sadhu SK, Ahmed F and Ishibashi M: Calotropin: A cardenolide from calotropis gigantea that inhibits Wnt signaling by increasing casein kinase 1α in colon cancer cells. ChemBioChem 15: 872-878, 2014.
163. Li B, Flaveny CA, Giambelli C, Fei DL, Han L, Hang BI, Bai F, Pei XH, Nose V, Burlingame O, et al: Repurposing the FDA-approved pinworm drug pyrvinium as a novel chemotherapeutic agent for intestinal polyposis. PLoS One 9: e101969, 2014.
164. Wei W, Chua MS, Grepper S and So S: Small molecule antagonists of Tcf4/beta-catenin complex inhibit the growth of HCC cells in vitro and in vivo. Int J Cancer 126: 2426-2436, 2010.
165. Lee SB, Gong YD, Park YI and Dong MS: 2,3,6-Trisubstituted quinoxaline derivative, a small molecule inhibitor of the Wnt/ beta-catenin signaling pathway, suppresses cell proliferation and enhances radiosensitivity in A549/Wnt2 cells. Biochem Biophys Res Commun 431: 746-752, 2013.
166. Preet R, Mohapatra P, Das D, Satapathy SR, Choudhuri T, Wyatt MD and Kundu CN: Lycopene synergistically enhances quinacrine action to inhibit Wnt-TCF signaling in breast cancer cells through APC. Carcinogenesis 34: 277-286, 2013.
167. Park S and Chun S: Streptonigrin inhibits β-catenin/Tcf signaling and shows cytotoxicity in β-catenin-activated cells. Biochim Biophys Acta 1810: 1340-1345, 2011.
168. Emami KH, Nguyen C, Ma H, Kim DH, Jeong KW, Eguchi M, Moon RT, Teo JL, Kim HY, Moon SH, et al: A small molecule inhibitor of beta-catenin/CREB-binding protein transcription [corrected]. Proc Natl Acad Sci USA 101: 12682-12687, 2004.
169. Yu SD, Liu FY and Wang QR: Notch inhibitor: A promising carcinoma radiosensitizer. Asian Pac J Cancer Prev 13: 5345-5351, 2012.
170. Wei W, Chua MS, Grepper S and So SK: Blockade of Wnt-1 signaling leads to anti-tumor effects in hepatocellular carcinoma cells. Mol Cancer 8: 76, 2009.
171. Mazieres J, You L, He B, Xu Z, Twogood S, Lee AY, Reguart N, Batra S, Mikami I and Jablons DM: Wnt2 as a new therapeutic target in malignant pleural mesothelioma. Int J Cancer 117: 326-332, 2005.
172. Pode-Shakked N, Harari-Steinberg O, Haberman-Ziv Y, Rom-Gross E, Bahar S, Omer D, Metsuyanim S, Buzhor E, Jacob-Hirsch J, Goldstein RS, et al: Resistance or sensitivity of Wilms' tumor to anti-FZD7 antibody highlights the Wnt pathway as a possible therapeutic target. Oncogene 30: 1664-1680, 2011.