Current Understanding on EGFR and Wnt/β-Catenin Signaling in Glioma and Their Possible Crosstalk

Genes and Cancer

Volumn 4, Issue 11-12, 2013, Pages 427-446

  Paul, Indranil ^a   Bhattacharya, Seemana ^a   Chatterjee, Anirban ^a   Ghosh, Mrinal K ^a  

^a INDIAN INSTITUTE OF CHEMICAL BIOLOGY   (India)

Author keywords

catenin; crosstalk; EGFR; glioma; signaling

Indexed keywords

BETA CATENIN; CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE; EPIDERMAL GROWTH FACTOR RECEPTOR; GROWTH FACTOR RECEPTOR BOUND PROTEIN 2; GROWTH FACTOR RECEPTOR BOUND PROTEIN 7; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; JANUS KINASE; LYMPHOCYTE ANTIGEN; MAMMALIAN TARGET OF RAPAMYCIN; MATRIX METALLOPROTEINASE; MITOGEN ACTIVATED PROTEIN KINASE; NOTCH RECEPTOR; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3, 4, 5 TRISPHOSPHATE 3 PHOSPHATASE; PHOSPHOLIPASE C GAMMA; PLATELET DERIVED GROWTH FACTOR; PROTEIN TYROSINE PHOSPHATASE; RAF PROTEIN; RAS PROTEIN; STAT1 PROTEIN; SYNAPTOPHYSIN; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; VASCULOTROPIN; WNT PROTEIN;

CANCER GROWTH; CANCER SPECIFIC SURVIVAL; CANCER STEM CELL; CELL DIFFERENTIATION; CELL MIGRATION; CELL PROLIFERATION; DNA METHYLATION; GENE AMPLIFICATION; GENE EXPRESSION; GLIOMA; HUMAN; NONHUMAN; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION;

EID: 84891551331     PISSN: 19476019     EISSN: 19476027     Source Type: Journal    
DOI: 10.1177/1947601913503341     Document Type: Review

References (199)

1. Clarke J,Butowski N,Chang S.Recent advances in therapy for glioblastoma.Arch Neurol. 2010;67:279-83.
2. Comprehensive genomic characterization defines human glioblastoma genes and core pathways.Nature. 2008;455:1061-8.
3. Anastas JN,Moon RT.WNT signalling pathways as therapeutic targets in cancer.Nat Rev Cancer. 2013;13:11-26.
4. Holland JD,Klaus A,Garratt AN,Birchmeier W.Wnt signaling in stem and cancer stem cells.Curr Opin Cell Biol. 2013;25:254-64.
5. Curtin JC,Lorenzi MV.Drug discovery approaches to target Wnt signaling in cancer stem cells.Oncotarget. 2010;1:563-77.
6. Bogdan S,Klämbt C.Epidermal growth factor receptor signaling.Curr Biol. 2001;11:R292-5.
7. Batzer AG,Rotin D,Ureña JM,Skolnik EY,Schlessinger J.Hierarchy of binding sites for Grb2 and Shc on the epidermal growth factor receptor.Mol Cell Biol. 1994;14:5192-201.
8. Antonyak MA,Moscatello DK,Wong AJ.Constitutive activation of c-Jun N-terminal kinase by a mutant epidermal growth factor receptor.J Biol Chem. 1998;273:2817-22.
9. Krasinskas AM.EGFR signaling in colorectal carcinoma.Patholog Res Int. 2011;2011:932932.
10. Lowenstein EJ,Daly RJ,Batzer AG, et al.The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling.Cell. 1992;70:431-42.
11. Cavallo RA,Cox RT,Moline MM, et al.Drosophila Tcf and Groucho interact to repress Wingless signalling activity.Nature. 1998;395:604-8.
12. Brantjes H,Roose J,van De,Wetering M,Clevers H.All Tcf HMG box transcription factors interact with Groucho-related co-repressors.Nucleic Acids Res. 2001;29:1410-9.
13. Hasson P,Paroush Z.Crosstalk between the EGFR and other signalling pathways at the level of the global transcriptional corepressor Groucho/TLE.Br J Cancer. 2007;96:R21-5.
14. Datta SR,Dudek H,Tao X, et al.Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery.Cell. 1997;91:231-41.
15. Moscatello DK,Holgado-Madruga M,Emlet DR,Montgomery RB,Wong AJ.Constitutive activation of phosphatidylinositol 3-kinase by a naturally occurring mutant epidermal growth factor receptor.J Biol Chem. 1998;273:200-6.
16. Bowman T,Garcia R,Turkson J,Jove R.STATs in oncogenesis.Oncogene. 2000;19:2474-88.
17. Bromberg J,Darnell JE.The role of STATs in transcriptional control and their impact on cellular function.Oncogene. 2000;19:2468-73.
18. Kazansky AV,Rosen JM.Signal transducers and activators of transcription 5B potentiates v-Src-mediated transformation of NIH-3T3 cells.Cell Growth Differ. 2001;12:1-7.
19. Leaman DW,Pisharody S,Flickinger TW, et al.Roles of JAKs in activation of STATs and stimulation of c-fos gene expression by epidermal growth factor.Mol Cell Biol. 1996;16:369-75.
20. Huang PH,Xu AM,White FM.Oncogenic EGFR signaling networks in glioma.Sci Signal. 2009;2:re6.
21. Ghosh M,Sharma P,Harbor P,Rahaman S,Haque S.PI3K-AKT pathway negatively controls EGFR-dependent DNA-binding activity of Stat3 in glioblastoma multiforme cells.Oncogene. 2005;24:7290-300.
22. Ferrara N.Molecular and biological properties of vascular endothelial growth factor.J Mol Med (Berl). 1999;77:527-43.
23. Wells A,Ware MF,Allen FD,Lauffenburger DA.Shaping up for shipping out: PLCgamma signaling of morphology changes in EGF-stimulated fibroblast migration.Cell Motil Cytoskeleton. 1999;44:227-33.
24. Mischel PS,Cloughesy TF.Targeted molecular therapy of GBM.Brain Pathol. 2003;13:52-61.
25. Nakada M,Kita D,Watanabe T, et al.Aberrant signaling pathways in glioma.Cancers. 2011;3:3242-78.
26. Kuan CT,Wikstrand CJ,Bigner DD.EGF mutant receptor vIII as a molecular target in cancer therapy.Endocr Relat Cancer. 2001;8:83-96.
27. Ciesielski MJ,Fenstermaker RA.Oncogenic epidermal growth factor receptor mutants with tandem duplication: gene structure and effects on receptor function.Oncogene. 2000;19:810-20.
28. Frederick L,Wang XY,Eley G,James CD.Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas.Cancer Res. 2000;60:1383-7.
29. Jorissen RN,Walker F,Pouliot N,Garrett TPJ,Ward CW,Burgess AW.Epidermal growth factor receptor: mechanisms of activation and signalling.Exp Cell Res. 2003;284:31-53.
30. Belda-Iniesta C,de Castro Carpeño J,Sereno M,González-Barón M,Perona R.Epidermal growth factor receptor and glioblastoma multiforme: molecular basis for a new approach.Clin Transl Oncol. 2008;10:73-7.
31. Fenstermaker RA,Ciesielski MJ.EGFR intron recombination in human gliomas: inappropriate diversion of V(D)J recombination?.Curr Genomics. 2007;8:163-70.
32. Wang J,Zhao Q,Qi Q, et al.Gambogic acid-induced degradation of mutant p53 is mediated by proteasome and related to CHIP.J Cell Biochem. 2011;112:509-19.
33. Bessman NJ,Lemmon MA.Finding the missing links in EGFR.Nat Struct Mol Biol. 2012;19:1-3.
34. Arjona D,Bello MJ,Rey JA.EGFR intragenic loss and gene amplification in astrocytic gliomas.Cancer Genet Cytogenet. 2006;164:39-43.
35. Maxwell M,Naber SP,Wolfe HJ, et al.Coexpression of platelet-derived growth factor (PDGF) and PDGF-receptor genes by primary human astrocytomas may contribute to their development and maintenance.J Clin Invest. 1990;86:131-40.
36. Uhrbom L,Holland EC.Modeling gliomagenesis with somatic cell gene transfer using retroviral vectors.J Neurooncol. 2001;53:297-305.
37. Feldkamp MM,Lau N,Guha A.Signal transduction pathways and their relevance in human astrocytomas.J Neurooncol. 1997;35:223-48.
38. Liu W,James CD,Frederick L,Alderete BE,Jenkins RB.PTEN/MMAC1 mutations and EGFR amplification in glioblastomas.Cancer Res. 1997;57:5254-7.
39. Vivanco I,Sawyers CL.The phosphatidylinositol 3-kinase AKT pathway in human cancer.Nat Rev Cancer. 2002;2:489-501.
40. Rinkenbaugh AL,Baldwin AS.Monoallelic deletion of NFKBIA in glioblastoma: when less is more.Cancer Cell. 2011;19:163-5.
41. Aguirre A,Rubio ME,Gallo V.Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal.Nature. 2010;467:323-7.
42. Keith B,Simon MC.Hypoxia-inducible factors, stem cells, and cancer.Cell. 2007;129:465-72.
43. Jin X,Yin J,Kim SH, et al.EGFR-AKT-Smad signaling promotes formation of glioma stem-like cells and tumor angiogenesis by ID3-driven cytokine induction.Cancer Res. 2011;71:7125-34.
44. Carmeliet P,Jain RK.Angiogenesis in cancer and other diseases.Nature. 2000;407:249-57.
45. Chen HL,Pistollato F,Hoeppner DJ,Ni HT,McKay RDG,Panchision DM.Oxygen tension regulates survival and fate of mouse central nervous system precursors at multiple levels.Stem Cells. 2007;25:2291-301.
46. Soeda A,Park M,Lee D, et al.Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1alpha.Oncogene. 2009;28:3949-59.
47. Wang GL,Semenza GL.Characterization of hypoxia-inducible factor 1 and regulation of DNA binding activity by hypoxia.J Biol Chem. 1993;268:21513-8.
48. Soeda A,Inagaki A,Oka N, et al.Epidermal growth factor plays a crucial role in mitogenic regulation of human brain tumor stem cells.J Biol Chem. 2008;283:10958-66.
49. Pouysségur J,Dayan F,Mazure NM.Hypoxia signalling in cancer and approaches to enforce tumour regression.Nature. 2006;441:437-43.
50. Lorimer IA,Keppler-Hafkemeyer A,Beers RA,Pegram CN,Bigner DD,Pastan I.Recombinant immunotoxins specific for a mutant epidermal growth factor receptor: targeting with a single chain antibody variable domain isolated by phage display.Proc Natl Acad Sci U S A. 1996;93:14815-20.
51. Sampson JH,Akabani G,Archer GE, et al.Progress report of a phase I study of the intracerebral microinfusion of a recombinant chimeric protein composed of transforming growth factor (TGF)-alpha and a mutated form of the Pseudomonas exotoxin termed PE-38 (TP-38) for the treatment of malignant brain tumors.J Neurooncol. 2003;65:27-35.
52. Eller JL,Longo SL,Kyle MM,Bassano D,Hicklin DJ,Canute GW.Anti-epidermal growth factor receptor monoclonal antibody cetuximab augments radiation effects in glioblastoma multiforme in vitro and in vivo.Neurosurgery. 2005;56:155-62.
53. Belda-Iniesta C,de Castro Carpeño J,Saenz EC,Gutiérrez M,Perona R,Barón MG.Long term responses with cetuximab therapy in glioblastoma multiforme.Cancer Biol Ther. 2006;5:912-4.
54. Wersall P,Ohlsson I,Biberfeld P, et al.Intratumoral infusion of the monoclonal antibody, mAb 425, against the epidermal-growth-factor receptor in patients with advanced malignant glioma.Cancer Immunol Immunother. 1997;44:157-64.
55. Rich JN,Reardon DA,Peery T, et al.Phase II trial of gefitinib in recurrent glioblastoma.J Clin Oncol. 2004;22:133-42.
56. Janmaat ML,Giaccone G.Small-molecule epidermal growth factor receptor tyrosine kinase inhibitors.Oncologist. 2003;8:576-86.
57. Low S,Vougioukas VI,Hielscher T,Schmidt U,Unterberg A,Halatsch ME.Pathogenetic pathways leading to glioblastoma multiforme: association between gene expressions and resistance to erlotinib.Anticancer Res. 2008;28:3729-32.
58. Peereboom DM,Shepard DR,Ahluwalia MS, et al.Phase II trial of erlotinib with temozolomide and radiation in patients with newly diagnosed glioblastoma multiforme.J Neurooncol. 2010;98:93-9.
59. Rich JN,Sathornsumetee S,Keir ST, et al.ZD6474, a novel tyrosine kinase inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor, inhibits tumor growth of multiple nervous system tumors.Clin Cancer Res. 2005;11:8145-57.
60. Yiin JJ,Hu B,Schornack PA, et al.ZD6474, a multitargeted inhibitor for receptor tyrosine kinases, suppresses growth of gliomas expressing an epidermal growth factor receptor mutant, EGFRvIII, in the brain.Mol Cancer Ther. 2010;9:929-41.
61. Traxler P,Allegrini PR,Brandt R, et al.AEE788: a dual family epidermal growth factor receptor/ErbB2 and vascular endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and antiangiogenic activity.Cancer Res. 2004;64:4931-41.
62. Kesari S,Ramakrishna N,Sauvageot C,Stiles CD,Wen PY.Targeted molecular therapy of malignant gliomas.Curr Neurol Neurosci Rep. 2005;5:186-97.
63. Slichenmyer WJ,Elliott WL,Fry DW.CI-1033, a pan-erbB tyrosine kinase inhibitor.Semin Oncol. 2001;28:80-5.
64. Tanaka S,Louis DN,Curry WT,Batchelor TT,Dietrich J.Diagnostic and therapeutic avenues for glioblastoma: no longer a dead end?.Nat Rev Clin Oncol. 2012;10:14-26.
65. Kubota N,Okada S,Inada T,Ohnishi K,Ohnishi T.Wortmannin sensitizes human glioblastoma cell lines carrying mutant and wild type TP53 gene to radiation.Cancer Lett. 2000;161:141-7.
66. Shingu T,Yamada K,Hara N, et al.Growth inhibition of human malignant glioma cells induced by the PI3-K-specific inhibitor.J Neurosurg. 2003;98:154-61.
67. Geoerger B,Kerr K,Tang CB, et al.Antitumor activity of the rapamycin analog CCI-779 in human primitive neuroectodermal tumor/medulloblastoma models as single agent and in combination chemotherapy.Cancer Res. 2001;61:1527-32.
68. Dancey JE.Clinical development of mammalian target of rapamycin inhibitors.Hematol Oncol Clin North Am. 2002;16:1101-14.
69. Chang SM,Kuhn J,Wen P, et al.Phase I/pharmacokinetic study of CCI-779 in patients with recurrent malignant glioma on enzyme-inducing antiepileptic drugs. Invest New Drugs. 2004;22:427-35.
70. Graff JR,McNulty AM,Hanna KR, et al.The protein kinase Cβ-selective inhibitor, enzastaurin (LY317615. HCl), suppresses signaling through the AKT pathway, induces apoptosis, and suppresses growth of human colon cancer and glioblastoma xenografts.Cancer Res. 2005;65:7462-9.
71. Butowski N,Chang SM,Lamborn KR, et al.Enzastaurin plus temozolomide with radiation therapy in glioblastoma multiforme: a phase I study.Neuro Oncol. 2010;12:608-13.
72. Ziegler DS,Wright RD,Kesari S, et al.Resistance of human glioblastoma multiforme cells to growth factor inhibitors is overcome by blockade of inhibitor of apoptosis proteins.J Clin Invest. 2008;118:3109-22.
73. Khoshyomn S,Nathan D,Manske GC,Osler TM,Penar PL.Synergistic effect of genistein and BCNU on growth inhibition and cytotoxicity of glioblastoma cells.J Neurooncol. 2002;57:193-200.
74. Guha A,Feldkamp MM,Lau N,Boss G,Pawson A.Proliferation of human malignant astrocytomas is dependent on Ras activation.Oncogene. 1997;15:2755-65.
75. Wilcox ME,Yang W,Senger D, et al.Reovirus as an oncolytic agent against experimental human malignant gliomas.J Natl Cancer Inst. 2001;93:903-12.
76. Kanai R,Wakimoto H,Martuza RL,Rabkin SD.A novel oncolytic herpes simplex virus that synergizes with phosphoinositide 3-kinase/Akt pathway inhibitors to target glioblastoma stem cells.Clin Cancer Res. 2011;17:3686-96.
77. Lan F,Yue X,Han L, et al.Antitumor effect of aspirin in glioblastoma cells by modulation of β-catenin/T-cell factor-mediated transcriptional activity.J Neurosurg. 2011;115:780-8.
78. Luu HH,Zhang R,Haydon RC, et al.Wnt/beta-catenin signaling pathway as a novel cancer drug target.Curr Cancer Drug Targets. 2004;4:653-71.
79. Amado NG,Cerqueira DM,Menezes FS,da Silva JFM,Neto VM,Abreu JG.Isoquercitrin isolated from Hyptis fasciculata reduces glioblastoma cell proliferation and changes beta-catenin cellular localization.Anticancer Drugs. 2009;20:543-52.
80. Kim Y,Kim KH,Lee J, et al.Wnt activation is implicated in glioblastoma radioresistance.Lab Invest. 2012;92:466-73.
81. Kim EJ,Choi CH,Park JY,Kang SK,Kim YK.Underlying mechanism of quercetin-induced cell death in human glioma cells.Neurochem Res. 2008;33:971-9.
82. Siegelin MD,Reuss DE,Habel A,Rami A,von Deimling A.Quercetin promotes degradation of survivin and thereby enhances death-receptor-mediated apoptosis in glioma cells.Neuro Oncol. 2009;11:122-31.
83. Lim JH,Woo CH.Laminar flow activation of ERK5 leads to cytoprotective effect via CHIP-mediated p53 ubiquitination in endothelial cells.Anat Cell Biol. 2011;44:265-73.
84. Mimeault M,Batra SK.Potential applications of curcumin and its novel synthetic analogs and nanotechnology-based formulations in cancer prevention and therapy.Chin Med. 2011;6:31.
85. Wong HC,Bourdelas A,Krauss A, et al.Direct binding of the PDZ domain of Dishevelled to a conserved internal sequence in the C-terminal region of Frizzled.Mol Cell. 2003;12:1251-60.
86. Bilic J,Huang YL,Davidson G, et al.Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation.Science. 2007;316:1619-22.
87. Angers S,Moon RT.Proximal events in Wnt signal transduction.Nat Rev Mol Cell Biol. 2009;10:468-77.
88. MacDonald BT,Tamai K,He X.Wnt/beta-catenin signaling: components, mechanisms, and diseases.Dev Cell. 2009;17:9-26.
89. Fiedler M,Mendoza-Topaz C,Rutherford TJ,Mieszczanek J,Bienz M.Dishevelled interacts with the DIX domain polymerization interface of Axin to interfere with its function in down-regulating β-catenin.Proc Natl Acad Sci U S A. 2011;108:1937-42.
90. Clevers H,Nusse R.Wnt/β-catenin signaling and disease.Cell. 2012;149:1192-205.
91. Davidson G,Wu W,Shen J, et al.Casein kinase 1 gamma couples Wnt receptor activation to cytoplasmic signal transduction.Nature. 2005;438:867-72.
92. Zeng X,Tamai K,Doble B, et al.A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation.Nature. 2005;438:873-7.
93. Mi K,Dolan PJ,Johnson GVW.The low density lipoprotein receptor-related protein 6 interacts with glycogen synthase kinase 3 and attenuates activity.J Biol Chem. 2006;281:4787-94.
94. Cselenyi CS,Jernigan KK,Tahinci E,Thorne CA,Lee LA,Lee E.LRP6 transduces a canonical Wnt signal independently of Axin degradation by inhibiting GSK3's phosphorylation of beta-catenin.Proc Natl Acad Sci U S A. 2008;105:8032-7.
95. Piao S,Lee SH,Kim H, et al.Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling.PLoS One. 2008;3:e4046.
96. Wu G,Huang H,Garcia Abreu J,He X.Inhibition of GSK3 phosphorylation of beta-catenin via phosphorylated PPPSPXS motifs of Wnt coreceptor LRP6.PLoS One. 2009;4:e4926.
97. Taelman VF,Dobrowolski R,Plouhinec JL, et al.Wnt signaling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes.Cell. 2010;143:1136-48.
98. Wu X,Tu X,Joeng KS,Hilton MJ,Williams DA,Long F.Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling.Cell. 2008;133:340-53.
99. Cadigan KM.Wnt/beta-catenin signaling: turning the switch.Dev Cell. 2008;14:322-3.
100. Huang H,He X.Wnt/beta-catenin signaling: new (and old) players and new insights.Curr Opin Cell Biol. 2008;20:119-25.
101. Shitashige M,Hirohashi S,Yamada T.Wnt signaling inside the nucleus.Cancer Sci. 2008;99:631-7.
102. Mori T,Nagase H,Horii A, et al.Germ-line and somatic mutations of the APC gene in patients with Turcot syndrome and analysis of APC mutations in brain tumors.Genes Chromosomes Cancer. 1994;9:168-72.
103. Huang H,Mahler-Araujo BM,Sankila A, et al.APC mutations in sporadic medulloblastomas.Am J Pathol. 2000;156:433-7.
104. Yano H,Hara A,Shinoda J, et al.Immunohistochemical analysis of β-catenin in N-ethyl-N-nitrosourea-induced rat gliomas: implications in regulation of angiogenesis.Neurol Res. 2000;22:527-32.
105. Sareddy GR,Challa S,Panigrahi M,Babu PP.Wnt/beta-catenin/Tcf signaling pathway activation in malignant progression of rat gliomas induced by transplacental N-ethyl-N-nitrosourea exposure.Neurochem Res. 2009;34:1278-88.
106. Pu P,Zhang Z,Kang C, et al.Downregulation of Wnt2 and β-catenin by siRNA suppresses malignant glioma cell growth.Cancer Gene Ther. 2009;16:351-61.
107. Lu J,Zhang F,Zhao D, et al.ATRA-inhibited proliferation in glioma cells is associated with subcellular redistribution of β-catenin via up-regulation of Axin.J Neurooncol. 2008;87:271-7.
108. Lim ST,Miller NLG,Chen XL, et al.Nuclear-localized focal adhesion kinase regulates inflammatory VCAM-1 expression.J Cell Biol. 2012;197:907-19.
109. Liu X,Wang L,Zhao S,Ji X,Luo Y,Ling F.β-Catenin overexpression in malignant glioma and its role in proliferation and apoptosis in glioblastma cells.Med Oncol. 2011;28:608-14.
110. Rossi M,Magnoni L,Miracco C, et al.β-Catenin and Gli1 are prognostic markers in glioblastoma.Cancer Biol Ther. 2011;11:753-61.
111. Zhang N,Wei P,Gong A, et al.FoxM1 promotes β-catenin nuclear localization and controls Wnt target-gene expression and glioma tumorigenesis.Cancer Cell. 2011;20:427-42.
112. Gong A,Huang S.FoxM1 and Wnt/β-catenin signaling in glioma stem cells.Cancer Res. 2012;72:5658-62.
113. Hamilton SR,Liu B,Parsons RE, et al.The molecular basis of Turcot's syndrome.N Engl J Med. 1995;332:839-47.
114. Dahmen RP,Koch A,Denkhaus D, et al.Deletions of AXIN1, a component of the WNT/wingless pathway, in sporadic medulloblastomas.Cancer Res. 2001;61:7039-43.
115. Koch A,Hrychyk A,Hartmann W, et al.Mutations of the Wnt antagonist AXIN2 (Conductin) result in TCF-dependent transcription in medulloblastomas.Int J Cancer. 2007;121:284-91.
116. Pećina-Slaus N,Martić TN,Kokotović T,Kusec V,Tomas D,Hrasćan R.AXIN-1 protein expression and localization in glioblastoma.Coll Antropol. 2011;35:101-6.
117. Zhang LY,Ye J,Zhang F, et al.Axin induces cell death and reduces cell proliferation in astrocytoma by activating the p53 pathway.Int J Oncol. 2009;35:25-32.
118. Atkins RJ,Dimou J,Paradiso L, et al.Regulation of glycogen synthase kinase-3 beta (GSK-3β) by the Akt pathway in gliomas.J Clin Neurosci. 2012;19:1558-63.
119. Li Y,Lu H,Huang Y, et al.Glycogen synthase kinases-beta controls differentiation of malignant glioma cells.Int J Cancer. 2010;127:1271-82.
120. Kotliarova S,Pastorino S,Kovell LC, et al.Glycogen synthase kinase-3 inhibition induces glioma cell death through c-MYC, nuclear factor-kappaB, and glucose regulation.Cancer Res. 2008;68:6643-51.
121. Korur S,Huber RM,Sivasankaran B, et al.GSK3beta regulates differentiation and growth arrest in glioblastoma.PLoS One. 2009;4:e7443.
122. Guo G,Mao X,Wang P, et al.The expression profile of FRAT1 in human gliomas.Brain Res. 2010;1320:152-8.
123. Thomas GM,Frame S,Goedert M,Nathke I,Polakis P,Cohen P.A GSK3-binding peptide from FRAT1 selectively inhibits the GSK3-catalysed phosphorylation of axin and beta-catenin.FEBS Lett. 1999;458:247-51.
124. Culbert AA,Brown MJ,Frame S, et al.GSK-3 inhibition by adenoviral FRAT1 overexpression is neuroprotective and induces Tau dephosphorylation and beta-catenin stabilisation without elevation of glycogen synthase activity.FEBS Lett. 2001;507:288-94.
125. Guo G,Liu B,Zhong C, et al.FRAT1 expression and its correlation with pathologic grade, proliferation, and apoptosis in human astrocytomas.Med Oncol. 2011;28:1-6.
126. Guo G,Kuai D,Cai S, et al.Knockdown of FRAT1 Expression by RNA interference inhibits human glioblastoma cell growth, migration and invasion.PLoS One. 2013;8:e61206.
127. Polakis P.Wnt signaling and cancer.Genes Dev. 2000;14:1837-51.
128. Polakis P.The many ways of Wnt in cancer.Curr Opin Genet Dev. 2007;17:45-51.
129. Foltz G,Yoon JG,Lee H, et al.Epigenetic regulation of wnt pathway antagonists in human glioblastoma multiforme.Genes Cancer. 2010;1:81-90.
130. Yang Z,Wang Y,Fang J, et al.Expression and aberrant promoter methylation of Wnt inhibitory factor-1 in human astrocytomas.J Exp Clin Cancer Res. 2010;29:26.
131. Yang Z,Wang Y,Fang J, et al.Downregulation of WIF-1 by hypermethylation in astrocytomas.Acta Biochim Biophys Sin (Shanghai). 2010;42:418-25.
132. Lambiv WL,Vassallo I,Delorenzi M, et al.The Wnt inhibitory factor 1 (WIF1) is targeted in glioblastoma and has a tumor suppressing function potentially by induction of senescence.Neuro Oncol. 2011;13:736-47.
133. Slusarski DC,Corces VG,Moon RT.Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling.Nature. 1997;390:410-3.
134. Pandur P,Läsche M,Eisenberg LM,Kühl M.Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis.Nature. 2002;418:636-41.
135. Lu X,Borchers AGM,Jolicoeur C,Rayburn H,Baker JC,Tessier-Lavigne M.PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates.Nature. 2004;430:93-8.
136. Takada I,Mihara M,Suzawa M, et al.A histone lysine methyltransferase activated by non-canonical Wnt signalling suppresses PPAR-γ transactivation.Nat Cell Biol. 2007;9:1273-85.
137. Simons M,Mlodzik M.Planar cell polarity signaling: from fly development to human disease.Annu Rev Genet. 2008;42:517-40.
138. Reis M,Czupalla CJ,Ziegler N, et al.Endothelial Wnt/beta-catenin signaling inhibits glioma angiogenesis and normalizes tumor blood vessels by inducing PDGF-β expression.J Exp Med. 2012;209:1611-27.
139. Yu JM,Jun ES,Jung JS, et al.Role of Wnt5a in the proliferation of human glioblastoma cells.Cancer Lett. 2007;257:172-81.
140. Kamino M,Kishida M,Kibe T, et al.Wnt-5a signaling is correlated with infiltrative activity in human glioma by inducing cellular migration and MMP-2.Cancer Sci. 2011;102:540-8.
141. Pulvirenti T,Van Der Heijden M,Droms LA,Huse JT,Tabar V,Hall A.Dishevelled 2 signaling promotes self-renewal and tumorigenicity in human gliomas.Cancer Res. 2011;71:7280-90.
142. Ju R,Cirone P,Lin S,Griesbach H,Slusarski DC,Crews CM.Activation of the planar cell polarity formin DAAM1 leads to inhibition of endothelial cell proliferation, migration, and angiogenesis.Proc Natl Acad Sci U S A. 2010;107:6906-11.
143. Augustin I,Goidts V,Bongers A, et al.The Wnt secretion protein Evi/Gpr177 promotes glioma tumourigenesis.EMBO Mol Med. 2012;4:38-51.
144. Malanchi I,Peinado H,Kassen D, et al.Cutaneous cancer stem cell maintenance is dependent on beta-catenin signalling.Nature. 2008;452:650-3.
145. Galli R,Binda E,Orfanelli U, et al.Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma.Cancer Res. 2004;64:7011-21.
146. Singh SK,Hawkins C,Clarke ID, et al.Identification of human brain tumour initiating cells.Nature. 2004;432:396-401.
147. Brescia P,Richichi C,Pelicci G.Current strategies for identification of glioma stem cells: adequate or unsatisfactory?.J Oncol. 2012;2012:376894.
148. Dietrich J,Diamond EL,Kesari S.Glioma stem cell signaling: therapeutic opportunities and challenges.Expert Rev Anticancer Ther. 2010;10:709-22.
149. Natsume A,Kinjo S,Yuki K, et al.Glioma-initiating cells and molecular pathology: implications for therapy.Brain Tumor Pathol. 2011;28:1-12.
150. Fodde R,Brabletz T.Wnt/beta-catenin signaling in cancer stemness and malignant behavior.Curr Opin Cell Biol. 2007;19:150-8.
151. Kalani MYS,Cheshier SH,Cord BJ, et al.Wnt-mediated self-renewal of neural stem/progenitor cells.Proc Natl Acad Sci U S A. 2008;105:16970-5.
152. Zechner D,Fujita Y,Hülsken J, et al.beta-Catenin signals regulate cell growth and the balance between progenitor cell expansion and differentiation in the nervous system.Dev Biol. 2003;258:406-18.
153. Ayyanan A,Civenni G,Ciarloni L, et al.Increased Wnt signaling triggers oncogenic conversion of human breast epithelial cells by a Notch-dependent mechanism.Proc Natl Acad Sci U S A. 2006;103:3799-804.
154. Jin X,Jeon HY,Joo KM, et al.Frizzled 4 regulates stemness and invasiveness of migrating glioma cells established by serial intracranial transplantation.Cancer Res. 2011;71:3066-75.
155. Zheng H,Ying H,Wiedemeyer R, et al.PLAGL2 regulates Wnt signaling to impede differentiation in neural stem cells and gliomas.Cancer Cell. 2010;17:497-509.
156. Polakis P.Drugging Wnt signalling in cancer.EMBO J. 2012;31:2737-46.
157. Brunori M,Malerba M,Kashiwazaki H,Iggo R.Replicating adenoviruses that target tumors with constitutive activation of the wnt signaling pathway.J Virol. 2001;75:2857-65.
158. Lukashev AN,Fuerer C,Chen MJ,Searle P,Iggo R.Late expression of nitroreductase in an oncolytic adenovirus sensitizes colon cancer cells to the prodrug CB1954.Hum Gene Ther. 2005;16:1473-83.
159. Peerlinck I,Merron A,Baril P, et al.Targeted radionuclide therapy using a Wnt-targeted replicating adenovirus encoding the Na/I symporter.Clin Cancer Res. 2009;15:6595-601.
160. Zhang K,Zhang J,Han L,Pu P,Kang C.Wnt/beta-catenin signaling in glioma.J Neuroimmune Pharmacol. 2012;7:740-9.
161. Zeng G,Apte U,Cieply B,Singh S,Monga SP.siRNA-mediated β-catenin knockdown in human hepatoma cells results in decreased growth and survival.Neoplasia. 2007;9:951-9.
162. Ashihara E,Kawata E,Nakagawa Y, et al.β-Catenin small interfering RNA successfully suppressed progression of multiple myeloma in a mouse model.Clin Cancer Res. 2009;15:2731-8.
163. Yeung J,Esposito MT,Gandillet A, et al.β-Catenin mediates the establishment and drug resistance of MLL leukemic stem cells.Cancer Cell. 2010;18:606-18.
164. Lee JM,Kim IS,Kim H, et al.RORalpha attenuates Wnt/beta-catenin signaling by PKCalpha-dependent phosphorylation in colon cancer.Mol Cell. 2010;37:183-95.
165. Yue X,Lan F,Yang W, et al.Interruption of β-catenin suppresses the EGFR pathway by blocking multiple oncogenic targets in human glioma cells.Brain Res. 2010;1366:27-37.
166. Chen L,Huang K,Han L, et al.β-Catenin/Tcf-4 complex transcriptionally regulates AKT1 in glioma.Int J Oncol. 2011;39:883-90.
167. Armanious H,Gelebart P,Mackey J,Ma Y,Lai R.STAT3 upregulates the protein expression and transcriptional activity of β-catenin in breast cancer.Int J Clin Exp Pathol. 2010;3:654-64.
168. Tan X,Apte U,Micsenyi A, et al.Epidermal growth factor receptor: a novel target of the Wnt/beta-catenin pathway in liver.Gastroenterology. 2005;129:285-302.
169. Guturi KKN,Mandal T,Chatterjee A, et al.Mechanism of β-catenin-mediated transcriptional regulation of epidermal growth factor receptor expression in glycogen synthase kinase 3 β-inactivated prostate cancer cells.J Biol Chem. 2012;287:18287-96.
170. Lu Z,Ghosh S,Wang Z,Hunter T.Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of beta-catenin, and enhanced tumor cell invasion.Cancer Cell. 2003;4:499-515.
171. Yang M,Wang C,Zhu X, et al.E3 ubiquitin ligase CHIP facilitates Toll-like receptor signaling by recruiting and polyubiquitinating Src and atypical PKCzeta.J Exp Med. 2011;208:2099-112.
172. Jean C,Blanc A,Prade-Houdellier N, et al.Epidermal growth factor receptor/beta-catenin/T-cell factor 4/matrix metalloproteinase 1: a new pathway for regulating keratinocyte invasiveness after UVA irradiation.Cancer Res. 2009;69:3291-9.
173. Ji H,Wang J,Nika H, et al.EGF-induced ERK activation promotes CK2-mediated disassociation of alpha-Catenin from beta-Catenin and transactivation of beta-Catenin.Mol Cell. 2009;36:547-59.
174. Fang D,Hawke D,Zheng Y, et al.Phosphorylation of beta-catenin by AKT promotes beta-catenin transcriptional activity.J Biol Chem. 2007;282:11221-9.
175. Taurin S,Sandbo N,Qin Y,Browning D,Dulin NO.Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase.J Biol Chem. 2006;281:9971-6.
176. van Veelen W,Le NH,Helvensteijn W, et al.β-Catenin tyrosine 654 phosphorylation increases Wnt signalling and intestinal tumorigenesis.Gut. 2011;60:1204-12.
177. Suzuki M,Shigematsu H,Nakajima T, et al.Synchronous alterations of Wnt and epidermal growth factor receptor signaling pathways through aberrant methylation and mutation in non small cell lung cancer.Clin Cancer Res. 2007;13:6087-92.
178. Lee JH,Khadka P,Baek SH,Chung IK.CHIP promotes human telomerase reverse transcriptase degradation and negatively regulates telomerase activity.J Biol Chem. 2010;285:42033-45.
179. Rappl A,Piontek G,Schlegel J.EGFR-dependent migration of glial cells is mediated by reorganisation of N-cadherin.J Cell Sci. 2008;121:4089-97.
180. Yamoutpour F,Bodempudi V,Park SE, et al.Gene silencing for epidermal growth factor receptor variant III induces cell-specific cytotoxicity.Mol Cancer Ther. 2008;7:3586-97.
181. Baryawno N,Sveinbjörnsson B,Eksborg S,Chen CS,Kogner P,Johnsen JI.Small-molecule inhibitors of phosphatidylinositol 3-kinase/Akt signaling inhibit Wnt/beta-catenin pathway cross-talk and suppress medulloblastoma growth.Cancer Res. 2010;70:266-76.
182. Yang CH,Yue J,Fan M,Pfeffer LM.IFN induces miR-21 through a signal transducer and activator of transcription 3-dependent pathway as a suppressive negative feedback on IFN-induced apoptosis.Cancer Res. 2010;70:8108-16.
183. Zhou Y,Liu F,Xu Q,Wang X.Analysis of the expression profile of Dickkopf-1 gene in human glioma and the association with tumor malignancy.J Exp Clin Cancer Res. 2010;29:138.
184. Hide T,Takezaki T,Nakatani Y,Nakamura H,Kuratsu JI,Kondo T.Combination of a Ptgs2 inhibitor and an epidermal growth factor receptor-signaling inhibitor prevents tumorigenesis of oligodendrocyte lineage-derived glioma-initiating cells.Stem Cells. 2011;29:590-9.
185. Nager Grifo M,Bhardwaj D,Canti C,Medina L,Nogués P,Herreros J.β-Catenin signalling in glioblastoma multiforme and glioma-initiating cells.Chemother Res Pract. 2012;2012:192362.
186. Katoh M,Katoh M.STAT3-induced WNT5A signaling loop in embryonic stem cells, adult normal tissues, chronic persistent inflammation, rheumatoid arthritis and cancer.Int J Mol Med. 2007;19:273-8.
187. Kang MI,Baker AR,Dextras CR,Cabarcas SM,Young MR,Colburn NH.Targeting of noncanonical Wnt5a signaling by AP-1 blocker dominant-negative Jun when it inhibits skin carcinogenesis.Genes Cancer. 2012;3:37-50.
188. Chearwae W,Bright JJ.PPARγ agonists inhibit growth and expansion of CD133+ brain tumour stem cells.Br J Cancer. 2008;99:2044-53.
189. Zander T,Kraus JA,Grommes C, et al.Induction of apoptosis in human and rat glioma by agonists of the nuclear receptor PPARgamma.J Neurochem. 2002;81:1052-60.
190. Seufert S,Coras R,Tränkle C, et al.PPAR gamma activators: off-target against glioma cell migration and brain invasion.PPAR Res. 2008;2008:513943.
191. Wan Z,Shi W,Shao B, et al.Peroxisome proliferator-activated receptor γ agonist pioglitazone inhibits β-catenin-mediated glioma cell growth and invasion.Mol Cell Biochem. 2011;349:1-10.
192. Jansson EA,Are A,Greicius G, et al.The Wnt/beta-catenin signaling pathway targets PPARγ activity in colon cancer cells.Proc Natl Acad Sci U S A. 2005;102:1460-5.
193. Lee SY,Hur GY,Jung KH, et al.PPAR-γ agonist increase gefitinib's antitumor activity through PTEN expression.Lung Cancer. 2006;51:297-301.
194. Mansure JJ,Nassim R,Chevalier S, et al.A novel mechanism of PPAR gamma induction via EGFR signalling constitutes rational for combination therapy in bladder cancer.PloS One. 2013;8:e55997.
195. Hegi ME,Diserens AC,Bady P, et al.Pathway analysis of glioblastoma tissue after preoperative treatment with the EGFR tyrosine kinase inhibitor gefitinib-a phase II trial.Mol Cancer Ther. 2011;10:1102-12.
196. Dubrovska A,Elliott J,Salamone RJ, et al.Combination therapy targeting both tumor-initiating and differentiated cell populations in prostate carcinoma.Clin Cancer Res. 2010;16:5692-702.
197. Diaz A,Leon K.Therapeutic approaches to target cancer stem cells.Cancers. 2011;3:3331-52.
198. Hu T,Li C.Convergence between Wnt-b-catenin and EGFR signaling in cancer.Mol Cancer. 2010;9:236.
199. Stockhausen M-T,Broholm H,Villingshøj M, et al.Maintenance of EGFR and EGFRvIII expressions in an in vivo and in vitro model of human glioblastoma multiforme.Exp Cell Res. 2011;317:1513-26.