Clinical and Translational Oncology

, Volume 11, Issue 7, pp 411–427 | Cite as

Wnt signalling and cancer stem cells

  • Jesús Espada
  • Moisés B. Calvo
  • Silvia Díaz-Prado
  • Vanessa Medina
Educational Series Molecular and Cellular Biology of Cancer

Abstract

Intracellular signalling mediated by secreted Wnt proteins is essential for the establishment of cell fates and proper tissue patterning during embryo development and for the regulation of tissue homeostasis and stem cell function in adult tissues. Aberrant activation of Wnt signalling pathways has been directly linked to the genesis of different tumours. Here, the components and molecular mechanisms implicated in the transduction of Wnt signal, along with important results supporting a central role for this signalling pathway in stem cell function regulation and carcinogenesis will be briefly reviewed.

Keywords

Wnt β-catenin APC Cancer Cancer stem cells 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Nusse R (2001) An ancient cluster of Wnt paralogues. Trends Genet 17:443PubMedCrossRefGoogle Scholar
  2. 2.
    Grigoryan T, Wend P, Klaus A, Birchmeier W (2008) Deciphering the function of canonical Wnt signals in development and disease: conditional loss- and gain-of-function mutations of beta-catenin in mice. Genes Dev 22:2308–2341PubMedCrossRefGoogle Scholar
  3. 3.
    Huang H, He X (2008) Wnt/beta-catenin signaling: new (and old) players and new insights. Curr Opin Cell Biol 20:119–125PubMedCrossRefGoogle Scholar
  4. 4.
    Ling L, Nurcombe V, Cool SM (2008) Wnt signaling controls the fate of mesenchymal stem cells. Gene 433:1–7PubMedCrossRefGoogle Scholar
  5. 5.
    Nusse R (2008) Wnt signaling and stem cell control. Cell Res 18:523–527PubMedCrossRefGoogle Scholar
  6. 6.
    Mosimann C, Hausmann G, Basler K (2009) Beta-catenin hits chromatin: regulation of Wnt target gene activation. Nat Rev Mol Cell Biol 10:276–286PubMedCrossRefGoogle Scholar
  7. 7.
    Li F, Chong ZZ, Maiese K (2005) Vital elements of the Wnt-frizzled signalling pathway in the nervous system. Curr Neurovasc Res 2:331–340PubMedCrossRefGoogle Scholar
  8. 8.
    Li F, Chong ZZ, Maiese K (2006) Winding through the WNT pathway during cellular development and demise. Histol Histopathol 21:103–124PubMedGoogle Scholar
  9. 9.
    Miller JR (2002) The Wnts. Genome Biol 3:reviews3001.1–3001.15Google Scholar
  10. 10.
    Reichsman F, Smith L, Cumberledge S (1996) Glycosaminoglycans can modulate extracellular localization of the wingless protein and promote signal transduction. J Cell Biol 135:819–827PubMedCrossRefGoogle Scholar
  11. 11.
    Shibamoto S, Higano K, Takada R et al (1998) Cytoskeletal reorganization by soluble Wnt-3a protein signalling. Genes Cells 3:659–670PubMedCrossRefGoogle Scholar
  12. 12.
    van den Heuvel M, Nusse R, Johnston P, Lawrence PA (1989) Distribution of the wingless gene product in Drosophila embryos: a protein involved in cell-cell communication. Cell 59:739–749PubMedCrossRefGoogle Scholar
  13. 13.
    Bejsovec A, Wieschaus E (1995) Signalling activities of the Drosophila wingless gene are separately mutable and appear to be transduced at the cell surface. Genetics 139:309–320PubMedGoogle Scholar
  14. 14.
    Moline MM, Southern C, Bejsovec A (1999) Directionality of wingless protein transport influences epidermal patterning in the Drosophila embryo. Development 126:4375–4384PubMedGoogle Scholar
  15. 15.
    Dubois L, Lecourtois M, Alexandre C et al (2001) Regulated endocytic routing modulates wingless signalling in Drosophila embryos. Cell 105:613–624PubMedCrossRefGoogle Scholar
  16. 16.
    Greco V, Hannus M, Eaton S (2001) Argosomes: a potential vehicle for the spread of morphogens through epithelia. Cell 106:633–645PubMedCrossRefGoogle Scholar
  17. 17.
    Simmonds AJ, dosSantos G, Livne-Bar I, Krause HM (2001) Apical localization of wingless transcripts is required for wingless signalling. Cell 105:197–207PubMedCrossRefGoogle Scholar
  18. 18.
    Wilkie GS, Davis I (2001) Drosophila wingless and pair-rule transcripts localize apically by dynein-mediated transport of RNA particles. Cell 105:209–219PubMedCrossRefGoogle Scholar
  19. 19.
    Axelrod JD, Miller JR, Shulman JM et al (1998) Differential recruitment of Dishevelled provides signalling specificity in the planar cell polarity and Wingless signalling pathways. Genes Dev 12:2610–2622PubMedCrossRefGoogle Scholar
  20. 20.
    Boutros M, Paricio N, Strutt DI, Mlodzik M (1998) Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signalling. Cell 94:109–118PubMedCrossRefGoogle Scholar
  21. 21.
    Itoh K, Brott BK, Bae GU, Ratcliffe MJ, Sokol SY (2005) Nuclear localization is required for Dishevelled function in Wnt/beta-catenin signalling. J Biol 4:3PubMedCrossRefGoogle Scholar
  22. 22.
    Patapoutian A, Reichardt LF (2000) Roles of Wnt proteins in neural development and maintenance. Curr Opin Neurobiol 10:392–399PubMedCrossRefGoogle Scholar
  23. 23.
    Seifert JR, Mlodzik M (2006) Frizzled/PCP signalling: a conserved mechanism regulating cell polarity and directed motility. Nat Rev Genet 8:126–138CrossRefGoogle Scholar
  24. 24.
    Ma L, Wang HY (2006) Suppression of cyclic GMP-dependent protein kinase is essential to the Wnt/GMP/Ca2+ pathway. J Biol Chem 281:30990–31001PubMedCrossRefGoogle Scholar
  25. 25.
    Schulte G, Bryja V (2007) The frizzled family of unconventional G-protein-coupled receptors. Trends Pharmacol Sci 28:518–525PubMedCrossRefGoogle Scholar
  26. 26.
    Foord SM, Bonner TI, Neubig RR et al (2005) International union of pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev 57:279–288PubMedCrossRefGoogle Scholar
  27. 27.
    Melkonyan HS, Chang WC, Shapiro JP et al (1997) SARPs: a family of secreted apoptosis-related proteins. Proc Natl Acad Sci USA 94:13636–13641PubMedCrossRefGoogle Scholar
  28. 28.
    Wilson C, Goberdhan DC, Steller H (1993) Dror, a potential neurotrophic receptor gene, encodes a Drosophila homolog of the vertebrate Ror family of Trk-related receptor tyrosine kinases. Proc Natl Acad Sci USA 90:7109–7113PubMedCrossRefGoogle Scholar
  29. 29.
    Song L, Fricker LD (1997) Cloning and expression of human carboxypeptidase Z, a novel metallocarboxypeptidase. J Biol Chem 272:10543–10550PubMedCrossRefGoogle Scholar
  30. 30.
    Yan W, Sheng N, Seto M, Morser J, Wu Q (1999) Corin, a mosaic transmembrane serine protease encoded by a novel cDNA from human heart. J Biol Chem 274:14926–14935PubMedCrossRefGoogle Scholar
  31. 31.
    Wehrli M, Dougan ST, Caldwell K et al (2000) Arrow encodes an LDL-receptor-related protein essential for Wingless signalling. Nature 407:527–530PubMedCrossRefGoogle Scholar
  32. 32.
    Mao J, Wang J, Liu B et al (2001) Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signalling pathway. Mol Cell 7:801–809PubMedCrossRefGoogle Scholar
  33. 33.
    Tolwinski NS, Wehrli M, Rives A et al (2003) Wg/Wnt signal can be transmitted through arrow/LRP5, 6 and Axin independently of Zw3/Gsk3-beta activity. Dev Cell 4:407–418PubMedCrossRefGoogle Scholar
  34. 34.
    Bejsovec A (2005) Wnt pathway activation: new relations and locations. Cell 120:11–14PubMedGoogle Scholar
  35. 35.
    Lu W, Yamamoto V, Ortega B, Baltimore D (2004) Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth. Cell 119:97–108PubMedCrossRefGoogle Scholar
  36. 36.
    Ching W, Nusse R (2006) A dedicated Wnt secretion factor. Cell 125:432–433PubMedCrossRefGoogle Scholar
  37. 37.
    Bänziger C, Soldini D, Schütt C et al (2006) Wntless, a conserved membrane protein dedicated to the secretion of Wnt proteins from signalling cells. Cell 125:509–522PubMedCrossRefGoogle Scholar
  38. 38.
    Bartscherer K, Pelte N, Ingelfinger D, Boutros M (2006) Secretion of Wnt ligands requires Evi, a conserved transmembrane protein. Cell 125:523–533PubMedCrossRefGoogle Scholar
  39. 39.
    Vergés M, Luton F, Gruber C et al (2004) The mammalian retromer regulates transcytosis of the polymeric immunoglobin receptor. Nat Cell Biol 6:763–769PubMedCrossRefGoogle Scholar
  40. 40.
    Coudreuse DY, Roel G, Betist MC et al (2006) Wnt gradient formation requires retromer function in Wnt-producing cells. Science 312:921–924PubMedCrossRefGoogle Scholar
  41. 41.
    Hsieh JC, Rattner A, Smallwood PM, Nathans J (1999) Biochemical characterization of Wnt-frizzled interactions using a soluble, biologically active vertebrate Wnt protein. Proc Natl Acad Sci USA 382:225–230Google Scholar
  42. 42.
    He X, Semenov M, Tamai K, Zeng X (2004) LDL receptor-related proteins 5 and 6 in Wnt/betacatenin signalling: arrows point the way. Development 131:1663–1677PubMedCrossRefGoogle Scholar
  43. 43.
    Zeng X, Tamai K, Doble B et al (2005) A dualkinase mechanism for Wnt co-receptor phosphorylation and activation. Nature 438: 873–877PubMedCrossRefGoogle Scholar
  44. 44.
    Forrester WC (2002) The Ror receptor tyrosine kinase family. Cell Mol Life Sci 59:83–96PubMedCrossRefGoogle Scholar
  45. 45.
    Oishi I, Suzuki H, Onishi N et al (2003) The receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a/JNK signalling pathway. Genes Cells 8:645–654PubMedCrossRefGoogle Scholar
  46. 46.
    Mikels AJ, Nusse R (2006) Purified Wnt5a protein activates or inhibits beta-catenin-TCF signalling depending on receptor context. PLoS Biol 4:e115PubMedCrossRefGoogle Scholar
  47. 47.
    Moon RT, Kimelman D (1998) From cortical rotation to organizer gene expression: toward a molecular explanation of axis specification in Xenopus. BioEssays 20:536–545PubMedCrossRefGoogle Scholar
  48. 48.
    Sumanas S, Strege P, Heasman J, Ekker SC (2000) The putative wnt receptor Xenopus frizzled-7 functions upstream of beta-catenin in vertebrate dorsoventral mesoderm patterning. Development 127:1981–1990PubMedGoogle Scholar
  49. 49.
    Reya T, Clevers H (2005) Wnt signalling in stem cells and cancer. Nature 434:843–850PubMedCrossRefGoogle Scholar
  50. 50.
    Korinek V, Barker N, Moerer P et al (1998) Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat Genet 19:379–383PubMedCrossRefGoogle Scholar
  51. 51.
    Kim KA, Kakitani M, Zhao J et al (2005) Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science 309:1256–1259PubMedCrossRefGoogle Scholar
  52. 52.
    van Genderen C, Okamura RM, Farinas I et al (1994) Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice. Genes Dev 8:2691–2703PubMedCrossRefGoogle Scholar
  53. 53.
    Alonso L, Fuchs E (2003) Stem cells in the skin: waste not, Wnt not. Genes Dev 17:1189–1200PubMedCrossRefGoogle Scholar
  54. 54.
    Huelsken J, Vogel R, Erdmann B et al (2001) beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell 105:533–545PubMedCrossRefGoogle Scholar
  55. 55.
    Lowry WE, Blanpain C, Nowak JA et al (2005) Defining the impact of beta-catenin/Tcf transactivation on epithelial stem cells. Genes Dev 19:1596–1611PubMedCrossRefGoogle Scholar
  56. 56.
    Reya T, Duncan AW, Ailles L et al (2003) A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 423:409–414PubMedCrossRefGoogle Scholar
  57. 57.
    Kishida M, Hino SI, Michiue T et al (2001) Synergistic activation of the Wnt signalling pathway by Dvl and casein kinase Iepsilon. J Biol Chem 276:33147–33155PubMedCrossRefGoogle Scholar
  58. 58.
    Ishitani T, Ninomiya-Tsuji J, Matsumoto K (2003) Regulation of lymphoid enhancer factor 1/T-cell factor by mitogen-activated protein kinase-related Nemo-like kinase-dependent phosphorylation in Wnt/beta-catenin signalling. Mol Cell Biol 23:1379–1389PubMedCrossRefGoogle Scholar
  59. 59.
    Graham NA, Asthagiri AR (2004) Epidermal growth factor-mediated T-cell factor/lymphoid enhancer factor transcriptional activity is essential but not sufficient for cell cycle progression in nontransformed mammary epithelial cells. J Biol Chem 279:23517–23524PubMedCrossRefGoogle Scholar
  60. 60.
    Li F, Chong ZZ, Maiese K (2006) Microglial integrity is maintained by erythropoietin through integration of Akt and its substrates of glycogen synthase kinase-3beta, beta-catenin, and nuclear factor-kappaB. Curr Neurovasc Res 3:187–201PubMedCrossRefGoogle Scholar
  61. 61.
    Chen AE, Ginty DD, Fan CM (2005) Protein kinase A signalling via CREB controls myogenesis induced by Wnt proteins. Nature 433:317–322PubMedCrossRefGoogle Scholar
  62. 62.
    D’Amico M, Hulit J, Amanatullah DF et al (2000) The integrin-linked kinase regulates the cyclin D1 gene through glycogen synthase kinase 3beta and cAMP-responsive element-binding protein-dependent pathways. J Biol Chem 275:32649–32657PubMedCrossRefGoogle Scholar
  63. 63.
    Kinoshita N, Iioka H, Miyakoshi A, Ueno N (2003) PKC delta is essential for Dishevelled function in a noncanonical Wnt pathway that regulates Xenopus convergent extension movements. Genes Dev 17:1663–1676PubMedCrossRefGoogle Scholar
  64. 64.
    Tu X, Joeng KS, Nakayama KI et al (2007) Noncanonical Wnt signalling through G protein-linked PKC delta activation promotes bone formation. Dev Cell 12:113–127PubMedCrossRefGoogle Scholar
  65. 65.
    Ouko L, Ziegler TR, Gu LH et al (2004) Wnt11 signalling promotes proliferation, transformation, and migration of IEC6 intestinal epithelial cells. J Biol Chem 279:26707–26715PubMedCrossRefGoogle Scholar
  66. 66.
    Kremenevskaja N, von Wasielewski R, Rao AS et al (2005) Wnt-5a has tumour suppressor activity in thyroid carcinoma. Oncogene 24: 2144–2154PubMedCrossRefGoogle Scholar
  67. 67.
    Dejmek J, Safholm A, Kamp Nielsen C et al (2006) Wnt-5a/Ca2+-induced NFAT activity is counteracted by Wnt-5a/Yes-Cdc42-casein kinase 1 signalling in human mammary epithelial cells. Mol Cell Biol 26:6024–6036PubMedCrossRefGoogle Scholar
  68. 68.
    Safholm A, Leandersson K, Dejmek J et al (2006) A formylated hexapeptide ligand mimics the ability of Wnt-5a to impair migration of human breast epithelial cells. J Biol Chem 281:2740–2749PubMedCrossRefGoogle Scholar
  69. 69.
    Westfall TA, Brimeyer R, Twedt J et al (2003) Wnt-5/pipetail functions in vertebrate axis formation as a negative regulator of Wnt/beta-catenin activity. J Cell Biol 162:889–898PubMedCrossRefGoogle Scholar
  70. 70.
    Ishitani T, Ninomiya-Tsuji J, Nagai S et al (1999) The TAK1-NLK-MAPK-related pathway antagonizes signalling between beta-catenin and transcription factor TCF. Nature 399:798–802PubMedCrossRefGoogle Scholar
  71. 71.
    Garriock RJ, Krieg PA (2007) Wnt11-R signalling regulates a calcium sensitive EMT event essential for dorsal fin development of Xenopus. Dev Biol 304:127–140PubMedCrossRefGoogle Scholar
  72. 72.
    De Calisto J, Araya C, Marchant L et al (2005) Essential role of non-canonical Wnt signalling in neural crest migration. Development 132:2587–2597PubMedCrossRefGoogle Scholar
  73. 73.
    Matsui T, Raya A, Kawakami Y et al (2005) Noncanonical Wnt signalling regulates midline convergence of organ primordial during zebrafish development. Genes Dev 19:164–175PubMedCrossRefGoogle Scholar
  74. 74.
    Jenny A, Reynolds-Kenneally J, Das G et al (2005) Diego and Prickle regulate Frizzled planar cell polarity signalling by competing for Dishevelled binding. Nat Cell Biol 7:691–697PubMedCrossRefGoogle Scholar
  75. 75.
    Strutt D (2003) Frizzled signalling and cell polarisation in Drosophila and vertebrates. Development 130:4501–4513PubMedCrossRefGoogle Scholar
  76. 76.
    Hikasa H, Shibata M, Hiratami I, Taira M (2002) The Xenopus receptor tyrosine kinase Xror2 modulates morphogenetic movements of the axial mesoderm and neuroectoderm via Wnt signalling. Development 129: 5227–5239PubMedGoogle Scholar
  77. 77.
    Wu C, Zeng Q, Blumer KJ, Muslin AJ (2000) RGS proteins inhibit Xwnt-8 signalling in Xenopus embryonic development. Development 127:2773–2784PubMedGoogle Scholar
  78. 78.
    Liu T, DeCostanzo AJ, Liu X et al (2001) G protein signalling from activated rat frizzled-1 to the beta-catenin-Lef-Tcf pathway. Science 292:1718–1722PubMedCrossRefGoogle Scholar
  79. 79.
    Katanaev VL, Ponzielli R, Semeriva M, Tomlinson A (2005) Trimeric G protein-dependent frizzled signalling in Drosophila. Cell 120:111–122PubMedCrossRefGoogle Scholar
  80. 80.
    Park E, Kim GH, Choi SC, Han JK (2006) Role of PKA as a negative regulator of PCP signalling pathway during Xenopus gastrulation movements. Dev Biol 292:344–357PubMedCrossRefGoogle Scholar
  81. 81.
    Hoang B, Moos M Jr, Vukicevic S, Luyten FP (1996) Primary structure and tissue distribution of FRZB, a novel protein related to Drosophila frizzled, suggest a role in skeletal morphogenesis. J Biol Chem 271:26131–26137PubMedCrossRefGoogle Scholar
  82. 82.
    Rattner A, Hsieh JC, Smallwood PM et al (1997) A family of secreted proteins contains homology to the cysteinerich ligand-binding domain of frizzled receptors. Proc Natl Acad Sci USA 94:2859–2863PubMedCrossRefGoogle Scholar
  83. 83.
    Bafico A, Gazit A, Pramila T et al (1999) Interaction of frizzled related protein (FRP) with Wnt ligands and the frizzled receptor suggests alternative mechanisms for FRP inhibition of Wnt signalling. J Biol Chem 274:16180–16187PubMedCrossRefGoogle Scholar
  84. 84.
    Lin K, Wang S, Julius MA et al (1997) The cysteine-rich frizzled domain of Frzb-1 is required and sufficient for modulation of Wnt signalling. Proc Natl Acad Sci USA 94:11196–11200PubMedCrossRefGoogle Scholar
  85. 85.
    Wawrzak D, Metioui M, Willems E et al (2007) Wnt3a binds to several sFRPs in the nanomolar range. Biochem Biophys Res Commun 357:1119–1123PubMedCrossRefGoogle Scholar
  86. 86.
    Wu W, Glinka A, Delius H, Niehrs C (2000) Mutual antagonism between dickkopf1 and dickkopf2 regulates Wnt/beta-catenin signalling. Curr Biol 10:1611–1614PubMedCrossRefGoogle Scholar
  87. 87.
    Lin X (2004) Functions of heparan sulfate proteoglycans in cell signalling during development. Development 131:6009–6021PubMedCrossRefGoogle Scholar
  88. 88.
    Fre S, Vignjevic D, Schoumacher M et al (2008) Epithelial morphogenesis and intestinal cancer: new insights in signalling mechanisms. Cancer Res 100:85–111CrossRefGoogle Scholar
  89. 89.
    Piters E, Boudin E, Hul WV (2008) Wnt signalling: a win for bone. Arch Biochem Biophys 473:112–116PubMedCrossRefGoogle Scholar
  90. 90.
    Hwang SG, Yu SS, Lee SW, Chun JS (2005) Wnt3a regulates chondrocyte differentiation via c-Jun/AP-1 pathway. FEBS Lett 579:4837–4842PubMedCrossRefGoogle Scholar
  91. 91.
    Guo X, Day TF, Jiang X et al (2004) Wnt/betacatenin signalling is sufficient and necessary for synovial joint formation. Genes Dev 18:2404–2417PubMedCrossRefGoogle Scholar
  92. 92.
    Hu H, Hilton MJ, Tu X et al (2005) Sequential roles of Hedgehog and Wnt signalling in osteoblast development. Development 132:49–60PubMedCrossRefGoogle Scholar
  93. 93.
    Huelsken J, Birchmeier W (2001) New aspects of Wnt signalling pathways in higher vertebrates. Curr Opin Genet Dev 11:547–553PubMedCrossRefGoogle Scholar
  94. 94.
    Nusse R (1999) Wnt targets. Repression and activation. Trends Genet 15:1–3CrossRefGoogle Scholar
  95. 95.
    Giles RH, van Es JH, Clevers H (2003) Caught up in a Wnt storm: Wnt signalling in cancer. Biochim Biophys Acta 1653:1–24PubMedGoogle Scholar
  96. 96.
    Howe LR, Crawford HC, Subbaramaiah K et al (2001) PEA3 is up-regulated in response to Wnt1 and activates the expression of cyclooxygenase-2. J Biol Chem 276:20108–20115PubMedCrossRefGoogle Scholar
  97. 97.
    van de Wetering M, Sancho E, Verweij C et al (2002) The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111:241–250PubMedCrossRefGoogle Scholar
  98. 98.
    Wu S, Cetinkaya C, Munoz-Alonso MJLN et al (2003) Myc represses differentiation-induced p21CIP1 expression via Miz-1-dependent interaction with the p21 core promoter. Oncogene 22:351–360PubMedCrossRefGoogle Scholar
  99. 99.
    Tice DA, Soloviev I, Polakis P (2002) Activation of the Wnt pathway interferes with serum response element-driven transcription of immediate early genes. J Biol Chem 277:6118–6123PubMedCrossRefGoogle Scholar
  100. 100.
    Staal FJ, Weerkamp F, Baert MR et al (2004) Wnt target genes identified by DNA microarrays in immature CD34+ thymocytes regulate proliferation and cell adhesion. J Immunol 172:1099–1108PubMedGoogle Scholar
  101. 101.
    Jacobson AM, Musen G, Ryan CM et al (2007) Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med 356:1842–1852PubMedCrossRefGoogle Scholar
  102. 102.
    Maiese K, Chong ZZ, Shang YC (2007) Mechanistic insights into diabetes mellitus and oxidative stress. Curr Med Chem 14:1689–1699CrossRefGoogle Scholar
  103. 103.
    Monnier L, Mas E, Ginet C et al (2006) Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 295:1681–1687PubMedCrossRefGoogle Scholar
  104. 104.
    Rachek LI, Thornley NP, Grishko VI et al (2006) Protection of INS-1 cells from free fatty acidinduced apoptosis by targeting hOGG1 to mitochondria. Diabetes 55:1022–1028PubMedCrossRefGoogle Scholar
  105. 105.
    Pospisilik JA, Knauf C, Joza N et al (2007) Targeted deletion of AIF decreases mitochondrial oxidative phosphorylation and protects from obesity and diabetes. Cell 131:476–491PubMedCrossRefGoogle Scholar
  106. 106.
    Lehman DM, Hunt KJ, Leach RJ et al (2007) Haplotypes of transcription factor 7-like 2 (TCF7L2) gene and its upstream region are associated with type 2 diabetes and age of onset in Mexican Americans. Diabetes 56:389–393PubMedCrossRefGoogle Scholar
  107. 107.
    Guo YF, Xiong DH, Shen H et al (2006) Polymorphisms of the low-density lipoprotein receptorrelated protein 5 (LRP5) gene are associated with obesity phenotypes in a large family-based association study. J Med Genet 43:798–803PubMedCrossRefGoogle Scholar
  108. 108.
    Mani A, Radhakrishnan J, Wang H et al (2007) LRP6 mutation in a family with early coronary disease and metabolic risk factors. Science 315:1278–1282PubMedCrossRefGoogle Scholar
  109. 109.
    Aslanidi G, Kroutov V, Philipsberg G et al (2007) Ectopic expression of Wnt10b decreases adiposity and improves glucose homeostasis in obese rats. Am J Physiol Endocrinol Metab 293: E726–E736PubMedCrossRefGoogle Scholar
  110. 110.
    Maiese K, Li F, Chong ZZ (2004) Erythropoietin in the brain: can the promise to protect be fulfilled? Trends Pharmacol Sci 25:577–583PubMedCrossRefGoogle Scholar
  111. 111.
    Maiese K, Li F, Chong ZZ (2005) New avenues of exploration for erythropoietin. JAMA 293:90–95PubMedCrossRefGoogle Scholar
  112. 112.
    Chong ZZ, Shang YC, Maiese K (2007) Vascular injury during elevated glucose can be mitigated by erythropoietin and Wnt signalling. Curr Neurovasc Res 4:194–204PubMedCrossRefGoogle Scholar
  113. 113.
    Li F, Chong ZZ, Maiese K (2005) Vital elements of the Wnt-frizzled signalling pathway in the nervous system. Curr Neurovasc Res 2:331–340PubMedCrossRefGoogle Scholar
  114. 114.
    Li F, Chong ZZ, Maiese K (2006) Winding through the WNT pathway during cellular development and demise. Histol Histopathol 21:103–124PubMedGoogle Scholar
  115. 115.
    Morin PJ, Medina M, Semenov M et al (2004) Wnt-1 expression in PC12 cells induces exon 15 deletion and expression of L-APP. Neurobiol Dis 16:59–67PubMedCrossRefGoogle Scholar
  116. 116.
    Mudher A, Chapman S, Richardson J et al (2001) Dishevelled regulates the metabolism of amyloid precursor protein via protein kinase C/mitogenactivated protein kinase and c-Jun terminal kinase. J Neurosci 21:4987–4995PubMedGoogle Scholar
  117. 117.
    Salins P, Shawesh S, He Y et al (2007) Lovastatin protects human neurons against Abeta-induced toxicity and causes activation of beta-catenin-TCF/LEF signalling. Neurosci Lett 412:211–216PubMedCrossRefGoogle Scholar
  118. 118.
    Barandon L, Couffinhal T, Ezan J et al (2003) Reduction of infarct size and prevention of cardiac rupture in transgenic mice overexpressing FrzA. Circulation 108:2282–2289PubMedCrossRefGoogle Scholar
  119. 119.
    van de Schans VA, van den Borne SW, Strzelecka AE et al (2007) Interruption of Wnt signalling attenuates the onset of pressure overload-induced cardiac hypertrophy. Hypertension 49:473–480PubMedCrossRefGoogle Scholar
  120. 120.
    Kinzler KW, Nilbert MC, Su LK et al (1991) Identification of FAP locus genes from chromosome 5q21. Science 253:661–665PubMedCrossRefGoogle Scholar
  121. 121.
    Nishisho I, Nakamura Y, Miyoshi Y et al (1991) Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 253:665–669PubMedCrossRefGoogle Scholar
  122. 122.
    Korinek V, Barker N, Morin PJ et al (1997) Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Science 275:1784–1787PubMedCrossRefGoogle Scholar
  123. 123.
    Morin PJ, Sparks AB, Korinek V et al (1997) Activation of beta-catenin-Tcf signalling in colon cancer by mutations in beta-catenin or APC. Science 275:1787–1790PubMedCrossRefGoogle Scholar
  124. 124.
    Liang H, Chen Q, Coles AH et al (2003) Wnt5a inhibits B cell proliferation and functions as a tumour suppressor in hematopoietic tissue. Cancer Cell 4:349–360PubMedCrossRefGoogle Scholar
  125. 125.
    Polakis P (2000) Wnt signalling and cancer. Genes Dev 14:1837–1851PubMedGoogle Scholar
  126. 126.
    Aguilera O, Munoz A, Esteller M, Fraga MF (2007) Epigenetic alterations of the Wnt/beta-catenin pathway in human disease. Endocr Metab Immune Disord Drug Targets 7:13–21PubMedGoogle Scholar
  127. 127.
    Barker N, Clevers H (2006) Mining the Wnt pathway for cancer therapeutics. Nat Rev Drug Discov 5:997–1014PubMedCrossRefGoogle Scholar
  128. 128.
    Thun MJ, Henley SJ, Patrono C (2002) Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst 94:252–266PubMedGoogle Scholar
  129. 129.
    Castellone MD, Teramoto H, Williams BO et al (2005) Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signalling axis. Science 310:1504–1510PubMedCrossRefGoogle Scholar
  130. 130.
    Shao J, Jung C, Liu C, Sheng H (2005) Prostaglandin E2 Stimulates the beta-catenin/T cell factor-dependent transcription in colon cancer. J Biol Chem 280:26565–26572PubMedCrossRefGoogle Scholar
  131. 131.
    Soprano DR, Qin P, Soprano KJ (2004) Retinoic acid receptors and cancers. Annu Rev Nutr 24:201–221PubMedCrossRefGoogle Scholar
  132. 132.
    Shah S, Hecht A, Pestell R, Byers SW (2003) Trans-repression of beta-catenin activity by nuclear receptors. J Biol Chem 278:48137–48145PubMedCrossRefGoogle Scholar
  133. 133.
    Xiao JH, Ghosn C, Hinchman C et al (2003) Adenomatous polyposis coli (APC)-independent regulation of beta-catenin degradation via a retinoid X receptor-mediated pathway. J Biol Chem 278:29954–29962PubMedCrossRefGoogle Scholar
  134. 134.
    Palmer HG, Larriba MJ, Garcia JM et al (2004) The transcription factor SNAIL represses vitamin D receptor expression and responsiveness in human colon cancer. Nat Med 10:917–919PubMedCrossRefGoogle Scholar
  135. 135.
    Shah S, Islam MN, Dakshanamurthy S et al (2006) The molecular basis of vitamin D receptor and beta-catenin crossregulation. Mol Cell 21:799–809PubMedCrossRefGoogle Scholar
  136. 136.
    Jordan CT (2009) Cancer stem cells: controversial or just misunderstood? Cell Stem Cell 4:203–205PubMedCrossRefGoogle Scholar

Copyright information

© Feseo 2009

Authors and Affiliations

  • Jesús Espada
    • 1
  • Moisés B. Calvo
    • 2
  • Silvia Díaz-Prado
    • 3
  • Vanessa Medina
    • 4
  1. 1.Biomedical Research Institute “Alberto Sols” (CSIC-UAM)MadridSpain
  2. 2.Biomedical Research Institute of A Coruña (INIBIC)A CoruñaSpain
  3. 3.Medicine DepartmentUniversity of A CoruñaA CoruñaSpain
  4. 4.Oncology Research UnitA Coruña Universtiy HospitalA CoruñaSpain

Personalised recommendations