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A Wnt-er Wonderland—The complexity of Wnt signaling in melanoma

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Abstract

Wnt signaling is a complex process that requires the interplay of several different proteins. In addition to a large cohort of Wnt ligands, and frizzled receptors, some Wnt pathways also require the presence of co-receptors. Wnt ligands may activate one of three pathways, the canonical pathway, involving β -catenin, the planar cell polarity pathway and the Wnt/ calcium pathway. All three pathways have different results for the cells in which they signal. Aberrant activation of these pathways can lead to the development and progression of several cancers. In this review we will discuss the different Wnt pathways, and their contribution to melanoma progression.

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References

  1. Rijsewijk F, Schuermann M, Wagenaar E, Parren P, Weigel D, Nusse R: The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless. Cell 50: 649–657, 1987

    Google Scholar 

  2. Morin PJ, Weeraratna AT: Wnt signaling in human cancer. Cancer Treat Res 115: 169–187, 2003

    Google Scholar 

  3. Smolich BD, McMahon JA, McMahon AP, Papkoff J: Wnt family proteins are secreted and associated with the cell surface. Mol Biol Cell 4: 1267–1275, 1993

    Google Scholar 

  4. Tanaka K, Okabayashi K, Asashima M, Perrimon N, Kadowaki T: The evolutionarily conserved porcupine gene family is involved in the processing of the Wnt family. Eur J Biochem 267: 4300–4311, 2000

    Google Scholar 

  5. Tanaka K, Kitagawa Y, Kadowaki T: Drosophila segment polarity gene product porcupine stimulates the posttranslational N-glycosylation of wingless in the endoplasmic reticulum. J Biol Chem 277: 12816–12823, 2002

    Google Scholar 

  6. Willert K, Brown JD, Danenberg E, Duncan AW, Weissman IL, Reya T, Yates JR, 3rd, Nusse R: Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature 423: 448–452, 2003

    Google Scholar 

  7. Jue SF, Bradley RS, Rudnicki JA, Varmus HE, Brown AM: The mouse Wnt-1 gene can act via a paracrine mechanism in transformation of mammary epithelial cells. Mol Cell Biol 12: 321–328, 1992

    Google Scholar 

  8. Shimizu H, Julius MA, Giarre M, Zheng Z, Brown AM, Kitajewski J: Transformation by Wnt family proteins correlates with regulation of beta-catenin. Cell Growth Differ 8: 1349–1358, 1997

    Google Scholar 

  9. McMahon AP, Bradley A: The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain. Cell 62: 1073–1085, 1990

    Google Scholar 

  10. Monkley SJ, Delaney SJ, Pennisi DJ, Christiansen JH, Wainwright BJ: Targeted disruption of the Wnt2 gene results in placentation defects. Development 122: 3343–3353, 1996

    Google Scholar 

  11. Liu P, Wakamiya M, Shea MJ, Albrecht U, Behringer RR, Bradley A: Requirement for Wnt3 in vertebrate axis formation. Nat Genet 22: 361–365, 1999

    Google Scholar 

  12. Stark K, Vainio S, Vassileva G, McMahon AP: Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature 372: 679–683, 1994

    Google Scholar 

  13. Vainio S, Heikkila M, Kispert A, Chin N, McMahon AP: Female development in mammals is regulated by Wnt-4 signalling. Nature 397: 405–409, 1999

    Google Scholar 

  14. Yamaguchi TP, Bradley A, McMahon AP, Jones SA: Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development 126: 1211–1223, 1999

    Google Scholar 

  15. Cha KB, Douglas KR, Potok MA, Liang H, Jones SN, Camper SA: WNT5A signaling affects pituitary gland shape. Mech Dev 121: 183–194, 2004

    Google Scholar 

  16. Parr BA, McMahon AP: Sexually dimorphic development of the mammalian reproductive tract requires Wnt-7a. Nature 395: 707–710, 1998

    Google Scholar 

  17. Parr BA, McMahon AP: Dorsalizing signal Wnt-7a required for normal polarity of D-V and A-P axes of mouse limb. Nature 374: 350–353, 1995

    Google Scholar 

  18. Kauffman JS, Raff RA: Patterning mechanisms in the evolution of derived developmental life histories: the role of Wnt signaling in axis formation of the direct-developing sea urchin Heliocidaris erythrogramma. Dev Genes Evol 213: 612–624, 2003

    Google Scholar 

  19. Majumdar A, Vainio S, Kispert A, McMahon J, McMahon AP: Wnt11 and Ret/Gdnf pathways cooperate in regulating ureteric branching during metanephric kidney development. Development 130: 3175–3185, 2003

    Google Scholar 

  20. Gho M, Schweisguth F: Frizzled signalling controls orientation of asymmetric sense organ precursor cell divisions in Drosophila. Nature 393: 178–181, 1998

    Google Scholar 

  21. Slusarski DC, Corces VG, Moon RT: Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling. Nature 390: 410–413, 1997

    Google Scholar 

  22. Liu T, Liu X, Wang H, Moon RT, Malbon CC: Activation of rat frizzled-1 promotes Wnt signaling and differentiation of mouse F9 teratocarcinoma cells via pathways that require Galpha(q) and Galpha(o) function. J Biol Chem 274: 33539–33544, 1999

    Google Scholar 

  23. Malbon CC, Wang H, Moon RT: Wnt signaling and heterotrimeric G-proteins: Strange bedfellows or a classic romance? Biochem Biophys Res Commun 287: 589–593, 2001

    Google Scholar 

  24. Xu YK, Nusse R: The Frizzled CRD domain is conserved in diverse proteins including several receptor tyrosine kinases. Curr Biol 8: R405–406, 1998

    Google Scholar 

  25. Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet JP, He X: LDL-receptor-related proteins in Wnt signal transduction. Nature 407: 530–535, 2000

    Google Scholar 

  26. Wehrli M, Dougan ST, Caldwell K, O’Keefe L, Schwartz S, Vaizel-Ohayon D, Schejter E, Tomlinson A, DiNardo S: Arrow encodes an LDL-receptor-related protein essential for Wingless signalling. Nature 407: 527–530, 2000

    Google Scholar 

  27. Pandur P, Kuhl M: An arrow for wingless to take-offz Bioessays 23: 207–210, 2001

    Google Scholar 

  28. Pinson KI, Brennan J, Monkley S, Avery BJ, Skarnes WC : An LDL-receptor-related protein mediates Wnt signalling in mice. Nature 407: 535–538, 2000

    Google Scholar 

  29. Brennan K, Gonzalez-Sancho JM, Castelo-Soccio LA, Howe LR, Brown AM: Truncated mutants of the putative Wnt receptor LRP6/Arrow can stabilize beta-catenin independently of Frizzled proteins. Oncogene 23: 4873–4884, 2004

    Google Scholar 

  30. Schweizer L, Varmus H: Wnt/Wingless signaling through beta-catenin requires the function of both LRP/Arrow and frizzled classes of receptors. BMC Cell Biol 4: 4, 2003

    Google Scholar 

  31. Mao J, Wang J, Liu B, Pan W, Farr GH 3rd, Flynn C, Yuan H, Takada S, Kimelman D, Li L, Wu D: Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway. Mol Cell 7: 801–809, 2001

    Google Scholar 

  32. Takeda T, Yamazaki H, Farquhar MG: Identification of an apical sorting determinant in the cytoplasmic tail of megalin. Am J Physiol Cell Physiol 284: C1105–1113, 2003

    Google Scholar 

  33. Yoshikawa S, McKinnon RD, Kokel M, Thomas JB: Wnt-mediated axon guidance via the Drosophila Derailed receptor. Nature 422: 583–588, 2003

    Google Scholar 

  34. Patthy L: The WIF module. Trends Biochem Sci 25: 12–13, 2000

    Google Scholar 

  35. Oishi I, Suzuki H, Onishi N, Takada R, Kani S, Ohkawara B, Koshida I, Suzuki K, Yamada G, Schwabe GC, Mundlos S, Shibuya H, Takada S, Minami Y: The receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a/JNK signalling pathway. Genes Cells 8: 645–654, 2003

    Google Scholar 

  36. Kawano Y, Kypta R: Secreted antagonists of the Wnt signalling pathway. J Cell Sci 116: 2627–2634, 2003

    Google Scholar 

  37. Baranski M, Berdougo E, Sandler JS, Darnell DK, Burrus LW: The dynamic expression pattern of frzb-1 suggests multiple roles in chick development. Dev Biol 217: 25–41, 2000

    Google Scholar 

  38. Bafico A, Gazit A, Pramila T, Finch PW, Yaniv A, Aaronson SA: 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 274: 16180–16187, 1999

    Google Scholar 

  39. Hsieh JC, Kodjabachian L, Rebbert ML, Rattner A, Smallwood PM, Samos CH, Nusse R, Dawid IB, Nathans JA: New secreted protein that binds to Wnt proteins and inhibits their activities. Nature 398: 431–436, 1999

    Google Scholar 

  40. Glinka A, Wu W, Onichtchouk D, Blumenstock C, Niehrs C: Head induction by simultaneous repression of Bmp and Wnt signalling in Xenopus. Nature 389: 517–519, 1997

    Google Scholar 

  41. Mao B, Wu W, Davidson G, Marhold J, Li M, Mechler BM, Delius H, Hoppe D, Stannek P, Walter C, Glinka A, Niehrs C: Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling. Nature 417: 664–667, 2002

    Google Scholar 

  42. Gonzalez-Sancho JM, Brennan KR, Castelo-Soccio LA, 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

    Google Scholar 

  43. Morin PJ: Beta-catenin signaling and cancer. Bioessays 21: 1021–1030, 1999

    Google Scholar 

  44. Seidensticker MJ, Behrens J: Biochemical interactions in the wnt pathway. Biochim Biophys Acta 1495: 168–182, 2000

    Google Scholar 

  45. Behrens J, Jerchow BA, Wurtele M, Grimm J, Asbrand C, Wirtz R, Kuhl M, Wedlich D, Birchmeier W: Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta Science, 280: 596–599, 1998

    Google Scholar 

  46. Hart M, Concordet JP, Lassot I, Albert I, del los Santos R, Durand H, Perret C, Rubinfeld B, Margottin F, Benarous R, Polakis P: The F-box protein beta-TrCP associates with phosphorylated beta-catenin and regulates its activity in the cell. Curr Biol 9: 207–210, 1999

    Google Scholar 

  47. Jiang J, Struhl G: Regulation of the Hedgehog and Wingless signalling pathways by the F-box/WD40-repeat protein Slimb Nature, 391: 493–496, 1998

    Google Scholar 

  48. Liu T, DeCostanzo AJ, Liu X, Wang H, Hallagan S, Moon RT: Malbon C C G protein signaling from activated rat frizzled-1 to the beta-catenin-Lef-Tcf pathway. Science 292: 1718-1722, 2001

    Google Scholar 

  49. Peters JM, McKay RM, McKay JP, Graff JM: Casein kinase I transduces Wnt signals. Nature 401: 345–350, 1999

    Google Scholar 

  50. Willert K, Brink M, Wodarz A, Varmus H, Nusse R: Casein kinase 2 associates with and phosphorylates dishevelled. Embo J 16: 3089–3096, 1997

    Google Scholar 

  51. Itoh K, Antipova A, Ratcliffe MJ, Sokol S: Interaction of dishevelled and Xenopus axin-related protein is required for wnt signal transduction. Mol Cell Biol 20: 2228–2238, 2000

    Google Scholar 

  52. Willert K, Shibamoto S, Nusse R: Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex. Genes Dev 13: 1768–1773, 1999

    Google Scholar 

  53. Kishida S, Yamamoto H, Hino S, Ikeda S, Kishida M, Kikuchi A: DIX domains of Dvl and axin are necessary for protein interactions and their ability to regulate beta-catenin stability. Mol Cell Biol 19: 4414–4422, 1999

    Google Scholar 

  54. Li L, Yuan H, Weaver CD, Mao J, Farr GH 3rd, Sussman DJ, Jonkers J, Kimelman D, Wu D: Axin and Frat1 interact with dvl and GSK, bridging Dvl to GSK in Wnt-mediated regulation of LEF-1. Embo J 18: 4233–4240, 1999

    Google Scholar 

  55. Clevers H, van de Wetering M: TCF/LEF factor earn their wings. Trends Genet 13: 485–489, 1997

    Google Scholar 

  56. Giese K, Amsterdam A, Grosschedl R: DNA-binding properties of the HMG domain of the lymphoid-specific transcriptional regulator LEF-1. Genes Dev 5: 2567–2578, 1991

    Google Scholar 

  57. Giese K, Cox J, Grosschedl R: The HMG domain of lymphoid enhancer factor 1 bends DNA and facilitates assembly of functional nucleoprotein structures. Cell 69: 185–195, 1992

    Google Scholar 

  58. Hecht A, Litterst CM, Huber O, Kemler R: Functional characterization of multiple transactivating elements in beta-catenin, some of which interact with the TATA-binding protein in vitro. J Biol Chem 274: 18017–18025, 1999

    Google Scholar 

  59. Hsu SC, Galceran J, Grosschedl R: Modulation of transcriptional regulation by LEF-1 in response to Wnt-1 signaling and association with beta-catenin. Mol Cell Biol 18: 4807–4818, 1998

    Google Scholar 

  60. He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW: Identification of c-MYC as a target of the APC pathway. Science 281: 1509–1512, 1998

    Google Scholar 

  61. He TC, Chan TA, Vogelstein B, Kinzler KW: PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell 99: 335–345, 1999

    Google Scholar 

  62. Tetsu O, McCormick F: Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398: 422–426, 1999

    Google Scholar 

  63. Brabletz T, Jung A, Dag S, Hlubek F, Kirchner T: Beta-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer. Am J Pathol 155: 1033–1038, 1999

    Google Scholar 

  64. Mann B, Gelos M, Siedow A, Hanski ML, Gratchev A, Ilyas M, Bodmer WF, Moyer MP, Riecken EO, Buhr HJ, Hanski C: Target genes of beta-catenin-T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas. Proc Natl Acad Sci USA 96: 1603–1608, 1999

    Google Scholar 

  65. Strutt D: Frizzled signalling and cell polarisation in Drosophila and vertebrates. Development 130: 4501–4513, 2003

    Google Scholar 

  66. Moriguchi T, Kawachi K, Kamakura S, Masuyama N, Yamanaka H, Matsumoto K, Kikuchi A, Nishida E: Distinct domains of mouse dishevelled are responsible for the c-Jun N-terminal kinase/stress-activated protein kinase activation and the axis formation in vertebrates. J Biol Chem 274: 30957–30962, 1999

    Google Scholar 

  67. Yamanaka H, Moriguchi T, Masuyama N, Kusakabe M, Hanafusa H, Takada R, Takada S, Nishida E: JNK functions in the non-canonical Wnt pathway to regulate convergent extension movements in vertebrates. EMBO Rep 3: 69–75, 2002

    Google Scholar 

  68. Park M, Moon RT: The planar cell-polarity gene stbm regulates cell behaviour and cell fate in vertebrate embryos. Nat Cell Biol 4: 20–25, 2002

    Google Scholar 

  69. Feiguin F, Hannus M, Mlodzik M, Eaton S: The ankyrin repeat protein Diego mediates Frizzled-dependent planar polarization. Dev Cell 1: 93–101, 2001

    Google Scholar 

  70. Usui T, Shima Y, Shimada Y, Hirano S, Burgess RW, Schwarz TL, Takeichi M, Uemura T: Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled. Cell 98: 585–595, 1999

    Google Scholar 

  71. Axelrod JD, Miller JR, Shulman JM, Moon RT, Perrimon N: Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways. Genes Dev 12: 2610–2622, 1998

    Google Scholar 

  72. Strutt DI, Weber U, Mlodzik M: The role of RhoA in tissue polarity and Frizzled signalling. Nature 387: 292–295, 1997

    Google Scholar 

  73. Strutt D: Planar polarity: Getting ready to ROCK. Curr Biol 11: R506-509, 2001

    Google Scholar 

  74. Boutros M, Paricio N, Strutt DI, Mlodzik M: Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling. Cell 94: 109–118 1998

    Google Scholar 

  75. Strutt H, Strutt D: Nonautonomous planar polarity patterning in Drosophila: Dishevelled-independent functions of frizzled. Dev Cell 3: 851–863, 2002

    Google Scholar 

  76. Du SJ, Purcell SM, Christian JL, McGrew LL, Moon RT: Identification of distinct classes and functional domains of Wnts through expression of wild-type and chimeric proteins in Xenopus embryos. Mol Cell Biol 15: 2625–2634, 1995

    Google Scholar 

  77. Moon RT, Campbell RM, Christian JL, McGrew LL, Shih J, Fraser S Xwnt-5A: A maternal Wnt that affects morphogenetic movements after overexpression in embryos of Xenopus laevis. Development 119: 97–111, 1993

    Google Scholar 

  78. Jafri MS, Keizer J: On the roles of Ca2+ diffusion, Ca2+ buffers, and the endoplasmic reticulum in IP3-induced Ca2+ waves. Biophys J 69: 2139–2153, 1995

    Google Scholar 

  79. Kuhl M, Sheldahl LC, Malbon CC, Moon RT: Ca(2+)/calmodulin-dependent protein kinase II is stimulated by Wnt and Frizzled homologs and promotes ventral cell fates in Xenopus. J Biol Chem 275: 12701–12711, 2000

    Google Scholar 

  80. Kuhl M, Sheldahl LC, Park M, Miller JR, Moon RT: The Wnt/Ca2+ pathway: A new vertebrate Wnt signaling pathway takes shape. Trends Genet 16: 279–283, 2000

    Google Scholar 

  81. Sheldahl LC, Park M, Malbon CC, Moon RT: Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in a G-protein-dependent manner. Curr Biol 9: 695–698, 1999

    Google Scholar 

  82. Jonsson M, Smith K, Harris AL: Regulation of Wnt5a expression in human mammary cells by protein kinase C activity and the cytoskeleton. Br J Cancer 78: 430–438, 1998

    Google Scholar 

  83. He X, Saint-Jeannet JP, Wang Y, Nathans J, Dawid I, Varmus HA: Member of the Frizzled protein family mediating axis induction by Wnt-5A. Science 275: 1652–1654, 1997

    Google Scholar 

  84. Topol L, Jiang X, Choi H, Garrett-Beal L, Carolan PJ, Yang Y: Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent beta-catenin degradation. J Cell Biol 62: 899–908, 2003

    Google Scholar 

  85. Westfall TA, Brimeyer R, Twedt J, Gladon J, Olberding A, Furutani-Seiki M, Slusarski DC: Wnt-5/pipetail functions in vertebrate axis formation as a negative regulator of Wnt/beta-catenin activity. J Cell Biol 162: 889–898, 2003

    Google Scholar 

  86. Sheldahl LC, Slusarski DC, Pandur P, Miller JR, Kuhl M, Moon RT: Dishevelled activates Ca2+ flux, PKC, and CamKII in vertebrate embryos. J Cell Biol 161: 769–777, 2003

    Google Scholar 

  87. Yanfeng W, Saint-Jeannet JP, Klein PS: Wnt-frizzled signaling in the induction and differentiation of the neural crest. Bioessays 25: 317–325, 2003

    Google Scholar 

  88. Wu J, Saint-Jeannet JP, Klein PS: Wnt-frizzled signaling in neural crest formation. Trends Neurosci 26: 40–45, 2003

    Google Scholar 

  89. Saint-Jeannet JP, He X, Varmus HE, Dawid IB: Regulation of dorsal fate in the neuraxis by Wnt-1 and Wnt-3a. Proc Natl Acad Sci USA, 94: 13713–13718, 1997

    Google Scholar 

  90. Christiansen JH, Coles EG, Wilkinson DG: Molecular control of neural crest formation, migration and differentiation. Curr Opin Cell Biol 12: 719–724, 2000

    Google Scholar 

  91. LaBonne C: Vertebrate development: Wnt signals at the crest. Curr Biol 12: R743–744, 2002

    Google Scholar 

  92. Dunn KJ, Williams BO, Li Y, Pavan, WJ Neural: Crest-directed gene transfer demonstrates Wnt1 role in melanocyte expansion and differentiation during mouse development. Proc Natl Acad Sci USA 97: 10050–10055, 2000

    Google Scholar 

  93. Dorsky RI, Moon RT, Raible, DW: Control of neural crest cell fate by the Wnt signalling pathway Nature, 396: 370-373, 1998

    Google Scholar 

  94. Lewis JL, Bonner J, Modrell M, Ragland JW, Moon RT, Dorsky RI, Raible DW: Reiterated Wnt signaling during zebrafish neural crest development. Development 131: 1299–1308, 2004

    Google Scholar 

  95. Honore SM, Aybar MJ, Mayor R: Sox10 is required for the early development of the prospective neural crest in Xenopus embryos. Dev Biol 260: 79–96, 2003

    Google Scholar 

  96. Potterf SB, Mollaaghababa R, Hou L, Southard-Smith EM, Hornyak TJ, Arnheiter H, Pavan WJ: Analysis of SOX10 function in neural crest-derived melanocyte development: SOX10-dependent transcriptional control of dopachrome tautomerase. Dev Biol 237: 245–257, 2001

    Google Scholar 

  97. Potterf SB, Furumura M, Dunn KJ, Arnheiter H, Pavan W J: Transcription factor hierarchy in Waardenburg syndrome: Regulation of MITF expression by SOX10 and PAX3. Hum Genet 107: 1–6, 2000

    Google Scholar 

  98. Takeda K, Yasumoto K, Takada R, Takada S, Watanabe K, Udono T, Saito H, Takahashi K, Shibahara S: Induction of melanocyte-specific microphthalmia-associated transcription factor by Wnt-3a. J Biol Chem 275: 14013–14016, 2000

    Google Scholar 

  99. Herlyn M, Berking C, Li G, Satyamoorthy K: Lessons from melanocyte development for understanding the biological events in naevus and melanoma formation. Melanoma Res 10: 303–312, 2000

    Google Scholar 

  100. Pla P, Moore R, Morali OG, Grille S, Martinozzi S, Delmas V, Larue L: Cadherins in neural crest cell development and transformation. J Cell Physiol 189: 121–132, 2001

    Google Scholar 

  101. Morin PJ, Weeraratna AT: The APC tumor suppressor pathway. Methods Mol Biol 222: 21–40, 2003

    Google Scholar 

  102. Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, Kinzler KW: Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science 275: 1787–1790, 1997

    Google Scholar 

  103. Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E, Polakis P: Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science 275: 1790–1792, 1997

    Google Scholar 

  104. Pollock PM, Hayward N: Mutations in exon 3 of the beta-catenin gene are rare in melanoma cell lines. Melanoma Res 12: 183–186, 2002

    Google Scholar 

  105. Ruiter DJ, van Muijen GN: Markers of melanocytic tumour progression. J Pathol 186: 340–342, 1998

    Google Scholar 

  106. Worm J, Christensen C, Gronbaek K, Tulchinsky E, Guldberg P: Genetic and epigenetic alterations of the APC gene in malignant melanoma. Oncogene 23: 5215–5226, 2004

    Google Scholar 

  107. Demunter A, Libbrecht L, Degreef H, De Wolf-Peeters C, van den Oord JJ: Loss of membranous expression of beta-catenin is associated with tumor progression in cutaneous melanoma and rarely caused by exon 3 mutations. Mod Pathol 15: 454–461, 2002

    Google Scholar 

  108. Kielhorn E, Provost E, Olsen D, D’Aquila TG, Smith BL, Camp RL, Rimm DL: Tissue microarray-based analysis shows phospho-beta-catenin expression in malignant melanoma is associated with poor outcome. Int J Cancer 103: 652–656, 2003

    Google Scholar 

  109. Goodall J, Martinozzi S, Dexter TJ, Champeval D, Carreira S, Larue L, Goding CR: Brn-2 expression controls melanoma proliferation and is directly regulated by beta-catenin. Mol Cell Biol 24: 2915–2922, 2004

    Google Scholar 

  110. Robbins PF, El-Gamil M, Li YF, Kawakami Y, Loftus D, Appella E, Rosenberg SA: A mutated beta-catenin gene encodes a melanoma-specific antigen recognized by tumor infiltrating lymphocytes. J Exp Med 183: 1185–1192, 1996

    Google Scholar 

  111. Bittner M, Meltzer P, Chen Y, Jiang Y, Seftor E, Hendrix M, Radmacher M, Simon R, Yakhini Z, Ben-Dor A, Sampas N, Dougherty E, Wang E, Marincola F, Gooden C, Lueders J, Glatfelter A, Pollock P, Carpten J, Gillanders E, Leja D, Dietrich K, Beaudry C, Berens M, Alberts D, Sondak V: Molecular classification of cutaneous malignant melanoma by gene expression profiling. Nature 406: 536–540, 2000

    Google Scholar 

  112. Weeraratna AT, Jiang Y, Hostetter G, Rosenblatt K, Duray P, Bittner M, Trent JM: Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell 1: 279–288, 2002

    Google Scholar 

  113. Mapelli E, Banfi P, Sala E, Sensi M, Supino R, Zunino F, Gambetta RA: Effect of protein kinase C inhibitors on invasiveness of human melanoma clones expressing different levels of protein kinase C isoenzymes. Int J Cancer 57: 281–286, 1994

    Google Scholar 

  114. Pham K, Milovanovic T, Barr RJ, Truong T, Holcombe RF: Wnt ligand expression in malignant melanoma: Pilot study indicating correlation with histopathological features. Mol Pathol 56: 280–285, 2003

    Google Scholar 

  115. Perriton CL, Powles N, Chiang C, Maconochie MK, Cohn MJ: Sonic hedgehog signaling from the urethral epithelium controls external genital development. Dev Biol 247: 26–46, 2002

    Google Scholar 

  116. Choi SC, Han JK Xenopus Cdc42 regulates convergent extension movements during gastrulation through Wnt/Ca2+ signaling pathway. Dev Biol 244: 342–357, 2002

    Google Scholar 

  117. Clark EA, Golub TR, Lander E S, Hynes RO: Genomic analysis of metastasis reveals an essential role for RhoC. Nature 406: 532–535, 2000

    Google Scholar 

  118. Nakahara H, Otani T, Sasaki T, Miura Y, Takai Y, Kogo M: Involvement of Cdc42 and Rac small G proteins in invadopodia formation of RPMI7951 cells. Genes Cells 8: 1019–1027, 2003

    Google Scholar 

  119. Weeraratna AT, Becker D, Carr KM, Duray PH, Rosenblatt KP, Yang S, Chen Y, Bittner M, Strausberg RL, Riggins GJ, Wagner U, Kallioniemi OP, Trent JM, Morin PJ, Meltzer PS: Generation and analysis of melanoma SAGE libraries: SAGE advice on the melanoma transcriptome. Oncogene 23: 2264–2274, 2004

    Google Scholar 

  120. Bui TD, Tortora G, Ciardiello F, Harris AL: Expression of Wnt5a is downregulated by extracellular matrix and mutated c-Ha-ras in the human mammary epithelial cell line MCF-10A. Biochem Biophys Res Commun 239: 911–917, 1997

    Google Scholar 

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  1. Laboratory of Immunology, The National Institute on Aging, National Institutes of Health, Baltimore, MD

    Ashani T. Weeraratna

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Weeraratna, A.T. A Wnt-er Wonderland—The complexity of Wnt signaling in melanoma. Cancer Metastasis Rev 24, 237–250 (2005). https://doi.org/10.1007/s10555-005-1574-z

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