Journal of Molecular Medicine

, Volume 82, Issue 4, pp 223–231

Manipulation of glycogen-synthase kinase-3 activity in KSHV-associated cancers

Review
  • 115 Downloads

Abstract

The Kapsosi’s sarcoma-associated herpesvirus, KSHV, is associated with cancers that have increased incidence in patients who are also HIV positive or who have undergone organ transplantation. It has recently been observed that β-catenin is overexpressed in two KSHV-associated cancers, Kaposi’s sarcoma and primary effusion lymphoma. Investigation of the underlying defect in β-catenin regulation revealed that the KSHV-encoded LANA protein stabilizes β-catenin by binding to the negative regulator GSK-3, causing a cell-cycle-dependent nuclear accumulation of GSK-3. Thus, redistribution of GSK-3 has been identified as yet another mechanism through which β-catenin can be dysregulated and contribute to human cancer.

Keywords

Kaposi’s sarcoma-associated herpesvirus Latency-associated nuclear antigen GSK-3 β-Catenin Wnt pathway 

Abbreviations

APC

Adenomatous polyposis coli

cycD1

Cyclin D1

Dvl

Dishevelled

EBV

Epstein-Barr virus

FRAT

Frequently rearranged in advanced T cell lymphomas

GSK-3

Glycogen synthase kinase-3

KS

Kaposi’s sarcoma

KSHV

Kaposi’s sarcoma-associated herpesvirus

LANA

Latency-associated nuclear antigen

LEF

Lymphoid enhancer binding factor

PEL

Primary effusion lymphoma

Tcf

T-cell transcription factor

References

  1. 1.
    Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS (1994) Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 266:1865–1869PubMedGoogle Scholar
  2. 2.
    Ablashi DV, Chatlynne LG, Whitman JE, Jr., Cesarman E (2002) Spectrum of Kaposi’s sarcoma-associated herpesvirus, or human herpesvirus 8, diseases. Clin Microbiol Rev 15:439–464CrossRefPubMedGoogle Scholar
  3. 3.
    Schulz TF (2001) KSHV/HHV8-associated lymphoproliferations in the AIDS setting. Eur J Cancer 37:1217–1226CrossRefPubMedGoogle Scholar
  4. 4.
    Cool CD, Rai PR, Yeager ME, Hernandez-Saavedra D, Serls AE, Bull TM, Geraci MW, Brown KK, Routes JM, Tuder RM, Voelkel NF (2003) Expression of human herpesvirus 8 in primary pulmonary hypertension. N Engl J Med 349:1113–1122CrossRefPubMedGoogle Scholar
  5. 5.
    LaDuca JR, Love JL, Abbott LZ, Dube S, Freidman-Kien AE, Poiesz BJ (1998) Detection of human herpesvirus 8 DNA sequences in tissues and bodily fluids. J Infect Dis 178:1610–1615CrossRefPubMedGoogle Scholar
  6. 6.
    Pauk J, Huang ML, Brodie SJ, Wald A, Koelle DM, Schacker T, Celum C, Selke S, Corey L (2000) Mucosal shedding of human herpesvirus 8 in men. N Engl J Med 343:1369–1377Google Scholar
  7. 7.
    Euvrard S, Kanitakis J, Claudy A (2003) Skin cancers after organ transplantation. N Engl J Med 348:1681–1691CrossRefPubMedGoogle Scholar
  8. 8.
    Kedes DH, Oberskalski E, Busch M, Kohn R, Flood J, Ganem D (1996) The seroepidemiology of human herpesvirus 8 (Kaposi’s sarcoma-associated herpesvirus): distribution of infection in KS risk groups and evidence for sexual transmission. Nat Med 2:918–924PubMedGoogle Scholar
  9. 9.
    Gao S-J, Kingsley L, Li M, Zheng W, Parravicini C, Ziegler J, Newton R, Rinaldo CR, Saah A, Phair J, Detels R, Chang Y, Moore PS (1996) KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi’s sarcoma. Nat Med 2:925–928PubMedGoogle Scholar
  10. 10.
    Schulz TF (2000) KSHV (HHV8) infection. J Infect 41:125–129CrossRefPubMedGoogle Scholar
  11. 11.
    Boshoff C, Weiss RA (2001) Epidemiology and pathogenesis of Kaposi’s sarcoma-associated herpesvirus. Philos Trans R Soc Lond B Biol Sci 356:517–534PubMedGoogle Scholar
  12. 12.
    Simonart T, Hermans P, Schandene L, Van Vooren JP (2000) Phenotypic characteristics of Kaposi’s sarcoma tumour cells derived from patch-, plaque- and nodular-stage lesions: analysis of cell cultures isolated from AIDS and non-AIDS patients and review of the literature. Br J Dermatol 143:557–563PubMedGoogle Scholar
  13. 13.
    Nickoloff BJ (1993) PECAM-1 (CD31) is expressed on proliferating endothelial cells, stromal spindle-shaped cells, and dermal dendrocytes in Kaposi’s sarcoma. Arch Dermatol 129:250–251CrossRefPubMedGoogle Scholar
  14. 14.
    Weninger W, Partanen TA, Breiteneder-Geleff S, Mayer C, Kowalski H, Mildner M, Pammer J, Sturzl M, Kerjaschki D, Alitalo K, Tschachler E (1999) Expression of vascular endothelial growth factor receptor-3 and podoplanin suggests a lymphatic endothelial cell origin of Kaposi’s sarcoma tumor cells. Lab Invest 79:243–251PubMedGoogle Scholar
  15. 15.
    Pammer J, Plettenberg A, Weninger W, Diller B, Mildner M, Uthman A, Issing W, Sturzl M, Tschachler E (1996) CD40 antigen is expressed by endothelial cells and tumor cells in Kaposi’s sarcoma. Am J Pathol 148:1387–1396PubMedGoogle Scholar
  16. 16.
    Dupin N, Fisher C, Kellam P, Arid S, Tulliez M, Franck N, van Marck E, Salmon D, Gorin I, Escande JP, Weiss RA, Alitalo K, Boshoff C (1999) Distribution of human herpesvirus-8 latently infected cells in Kaposi’s sarcoma, multicentric Castleman’s disease, and primary effusion lymphoma. Proc Natl Acad Sci USA 96:4546–4551CrossRefPubMedGoogle Scholar
  17. 17.
    Matolcsy A, Nador RG, Cesarman E, Knowles DM (1998) Immunoglobulin VH gene mutational analysis suggests that primary effusion lymphomas derive from different stages of B cell maturation. Am J Pathol 153:1609–1614PubMedGoogle Scholar
  18. 18.
    Du MQ, Liu H, Diss TC, Ye H, Hamoudi RA, Dupin N, Meignin V, Oksenhendler E, Boshoff C, Isaacson PG (2001) Kaposi sarcoma-associated herpesvirus infects monotypic (IgM lambda) but polyclonal naive B cells in Castleman disease and associated lymphoproliferative disorders. Blood 97:2130–2136CrossRefPubMedGoogle Scholar
  19. 19.
    Russo JJ, Bohenzky RA, Chein M-C, Chen J, Yan M, Maddalena D, Parry JP, Peruzzi D, Edelman IS, Chang Y, Moore PS (1996) Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). Proc Natl Acad Sci USA 93:14862–14867CrossRefPubMedGoogle Scholar
  20. 20.
    Whitby D, Boshoff C (1998) Kaposi’s sarcoma herpesvirus as a new paradigm for virus-induced oncogenesis. Curr Opin Oncol 10:405–412PubMedGoogle Scholar
  21. 21.
    Moore PS, Chang Y (2001) Molecular virology of Kaposi’s sarcoma-associated herpesvirus. Philos Trans R Soc Lond B Biol Sci 356:499–516CrossRefPubMedGoogle Scholar
  22. 22.
    Choi J, Means RE, Damania B, Jung JU (2001) Molecular piracy of Kaposi’s sarcoma associated herpesvirus. Cytokine Growth Factor Rev 12:245–257CrossRefPubMedGoogle Scholar
  23. 23.
    Nicholas J, Zong J-C, Alcendor DJ, Ciufo DM, Poole LJ, Sarisky RT, Chiou CJ, Zhang X, Wan X, Guo H-G, Reitz MS, Hayward GS (1998) Novel organization features, captured cellular genes and strain variability within the genome of KSHV/HHV8. J Natl Cancer Inst Monogr 23:79–88PubMedGoogle Scholar
  24. 24.
    Jenner RG, Boshoff C (2002) The molecular pathology of Kaposi’s sarcoma-associated herpesvirus. Biochim Biophys Acta 1602:1–22CrossRefPubMedGoogle Scholar
  25. 25.
    Gao S-J, Boshoff C, Jayachandra S, Weiss RA, Chang Y, Moore PS (1997) KSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway. Oncogene 15:1979–1985CrossRefPubMedGoogle Scholar
  26. 26.
    Verschuren EW, Klefstrom J, Evan GI, Jones N (2002) The oncogenic potential of Kaposi’s sarcoma-associated herpesvirus cyclin is exposed by p53 loss in vitro and in vivo. Cancer Cell 2:229–241CrossRefPubMedGoogle Scholar
  27. 27.
    Montaner S, Sodhi A, Molinolo A, Bugge TH, Sawai ET, He Y, Li Y, Ray PE, Gutkind JS (2003) Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi’s sarcomagenesis and can promote the tumorigenic potential of viral latent genes. Cancer Cell 3:23–36PubMedGoogle Scholar
  28. 28.
    Young LS, Murray PG (2003) Epstein-Barr virus and oncogenesis: from latent genes to tumours. Oncogene 22:5108–5121CrossRefPubMedGoogle Scholar
  29. 29.
    Macsween KF, Crawford DH (2003) Epstein-Barr virus-recent advances. Lancet Infect Dis 3:131–140CrossRefPubMedGoogle Scholar
  30. 30.
    Cannon JS, Ciufo D, Hawkins AL, Griffin CA, Borowitz MJ, Hayward GS, Ambinder RF (2000) A new primary effusion lymphoma-derived cell line yields a highly infectious Kaposi’s sarcoma herpesvirus-containing supernatant. J Virol 74:10187–10193CrossRefPubMedGoogle Scholar
  31. 31.
    Chiou CJ, Poole LJ, Kim PS, Ciufo DM, Cannon JS, apRhys CM, Alcendor DJ, Zong JC, Ambinder RF, Hayward GS (2002) Patterns of gene expression and a transactivation function exhibited by the vGCR (ORF74) chemokine receptor protein of Kaposi’s sarcoma-associated herpesvirus. J Virol 76:3421–3439CrossRefPubMedGoogle Scholar
  32. 32.
    Parravicini C, Chandran B, Corbellino M, Berti E, Paulli M, Moore PS, Chang Y (2000) Differential viral protein expression in Kaposi’s sarcoma-associated herpesvirus-infected diseases: Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. Am J Pathol 156:743–749PubMedGoogle Scholar
  33. 33.
    Kirshner JR, Staskus K, Haase A, Lagunoff M, Ganem D (1999) Expression of the open reading frame 74 (G-protein-coupled receptor) gene of Kaposi’s sarcoma (KS)-associated herpesvirus: implications for KS pathogenesis. J Virol 73:6006–6014PubMedGoogle Scholar
  34. 34.
    Ballestas ME, Chatis PA, Kaye KM (1999) Efficient persistence of extrachromosomal KSHV DNA mediated by latency-associated nuclear antigen. Science 284:641–644CrossRefPubMedGoogle Scholar
  35. 35.
    Cotter MA II, Robertson ES (1999) The latency-associated nuclear antigen tethers the Kaposi’s sarcoma-associated herpesvirus genome to host chromosomes in body cavity-based lymphoma cells. Virology 264:254–264CrossRefPubMedGoogle Scholar
  36. 36.
    Krithivas A, Fujimuro M, Weidner M, Young DB, Hayward SD (2002) Protein interactions targeting the latency-associated nuclear antigen of Kaposi’s sarcoma-associated herpesvirus to cell chromosomes. J Virol 76:11596–11604CrossRefPubMedGoogle Scholar
  37. 37.
    Hu J, Garber AC, Renne R (2002) The latency-associated nuclear antigen of Kaposi’s sarcoma-associated herpesvirus supports latent DNA replication in dividing cells. J Virol 76:11677–11687CrossRefPubMedGoogle Scholar
  38. 38.
    Grundhoff A, Ganem D (2003) The latency-associated nuclear antigen of Kaposi’s sarcoma-associated herpesvirus permits replication of terminal repeat-containing plasmids. J Virol 77:2779–2783CrossRefPubMedGoogle Scholar
  39. 39.
    Fejer G, Medveczky MM, Horvath E, Lane B, Chang Y, Medveczky PG (2003) The latency-associated nuclear antigen of Kaposi’s sarcoma-associated herpesvirus interacts preferentially with the terminal repeats of the genome in vivo and this complex is sufficient for episomal DNA replication. J Gen Virol 84:1451–1462CrossRefPubMedGoogle Scholar
  40. 40.
    Garber AC, Hu J, Renne R (2002) Latency-associated nuclear antigen (LANA) cooperatively binds to two sites within the terminal repeat, and both sites contribute to the ability of LANA to suppress transcription and to facilitate DNA replication. J Biol Chem 277:27401–27411CrossRefPubMedGoogle Scholar
  41. 41.
    Shinohara H, Fukushi M, Higuchi M, Oie M, Hoshi O, Ushiki T, Hayashi J, Fujii M (2002) Chromosome binding site of latency-associated nuclear antigen of Kaposi’s sarcoma-associated herpesvirus is essential for persistent episome maintenance and is functionally replaced by histone H1. J Virol 76:12917–12924CrossRefPubMedGoogle Scholar
  42. 42.
    Friborg JJ, Kong W, Hottiger MO, Nabel GJ (1999) p53 inhibition by the LANA protein of KSHV protects against cell death. Nature 402:889–894PubMedGoogle Scholar
  43. 43.
    Radkov SA, Kellam P, Boshoff C (2000) The latent nuclear antigen of Kaposi sarcoma-associated herpesvirus targets the retinoblastoma-E2F pathway and with the oncogene H-ras transforms primary rat cells. Nat Med 6:1121–1127CrossRefPubMedGoogle Scholar
  44. 44.
    Fujimuro M, Wu FY, apRhys C, Kajumbula H, Young DB, Hayward GS, Hayward SD (2003) A novel viral mechanism for dysregulation of beta-catenin in Kaposi’s sarcoma-associated herpesvirus latency. Nat Med 9:300–306CrossRefPubMedGoogle Scholar
  45. 45.
    Fujimuro M, Hayward SD (2003) The latency-associated nuclear antigen of Kaposi’s sarcoma-associated herpesvirus manipulates the activity of glycogen synthase kinase-3beta. J Virol 77:8019–8030CrossRefPubMedGoogle Scholar
  46. 46.
    Woodgett JR (1990) Molecular cloning and expression of glycogen synthase kinase-3/factor A. EMBO J 9:2431–2438PubMedGoogle Scholar
  47. 47.
    Hoeflich KP, Luo J, Rubie EA, Tsao MS, Jin O, Woodgett JR (2000) Requirement for glycogen synthase kinase-3beta in cell survival and NF- kappaB activation. Nature 406:86–90CrossRefPubMedGoogle Scholar
  48. 48.
    Woodgett JR (2001) Judging a protein by more than its name: GSK-3. Sci STKE 18:RE12Google Scholar
  49. 49.
    Lustig B, Behrens J (2003) The Wnt signaling pathway and its role in tumor development. J Cancer Res Clin Oncol 129:199–221PubMedGoogle Scholar
  50. 50.
    Grimes CA, Jope RS (2001) The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling. Prog Neurobiol 65:391–426CrossRefPubMedGoogle Scholar
  51. 51.
    Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet JP, He X (2000) LDL-receptor-related proteins in Wnt signal transduction. Nature 407:530–535CrossRefPubMedGoogle Scholar
  52. 52.
    Wehrli M, Dougan ST, Caldwell K, O’Keefe L, Schwartz S, Vaizel-Ohayon D, Schejter E, Tomlinson A, DiNardo S (2000) Arrow encodes an LDL-receptor-related protein essential for Wingless signalling. Nature 407:527–530CrossRefPubMedGoogle Scholar
  53. 53.
    Mao J, Wang J, Liu B, Pan W, Farr GH, 3rd, Flynn C, Yuan H, Takada S, Kimelman D, Li L, Wu D (2001) Low-density lipoprotein receptor-related protein-5 binds to axin and regulates the canonical Wnt signaling pathway. Mol Cell 7:801–809CrossRefPubMedGoogle Scholar
  54. 54.
    Wharton KA, Jr (2003) Runnin’ with the Dvl: proteins that associate with Dsh/Dvl and their significance to Wnt signal transduction. Dev Biol 253:1–17CrossRefPubMedGoogle Scholar
  55. 55.
    Kim S, Lee J, Park J, Chung J (2003) BP75, bromodomain-containing M(r) 75,000 protein, binds dishevelled-1 and enhances Wnt signaling by inactivating glycogen synthase kinase-3 beta. Cancer Res 63:4792–4795PubMedGoogle Scholar
  56. 56.
    Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X, He X (2002) Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108:837–847PubMedGoogle Scholar
  57. 57.
    Aberle H, Bauer A, Stappert J, Kispert A, Kemler R (1997) Beta-catenin is a target for the ubiquitin-proteasome pathway. EMBO J 16:3797–3804PubMedGoogle Scholar
  58. 58.
    Amit S, Hatzubai A, Birman Y, Andersen JS, Ben-Shushan E, Mann M, Ben-Neriah Y, Alkalay I (2002) Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. Genes Dev 16:1066–1076CrossRefPubMedGoogle Scholar
  59. 59.
    Brantjes H, Barker N, van Es J, Clevers H (2002) TCF: Lady Justice casting the final verdict on the outcome of Wnt signalling. Biol Chem 383:255–261PubMedGoogle Scholar
  60. 60.
    Shtutman M, Zhurinsky J, Simcha I, Albanese C, D’Amico M, Pestell R, Ben-Ze’ev A (1999) The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Natl Acad Sci USA 96:5522–5527CrossRefPubMedGoogle Scholar
  61. 61.
    Tetsu O, McCormick F (1999) Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398:422–426PubMedGoogle Scholar
  62. 62.
    Conacci-Sorrell ME, Ben-Yedidia T, Shtutman M, Feinstein E, Einat P, Ben-Ze’ev A (2002) Nr-CAM is a target gene of the beta-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis. Genes Dev 16:2058–2072CrossRefPubMedGoogle Scholar
  63. 63.
    He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW (1998) Identification of c-MYC as a target of the APC pathway. Science 281:1509–1512CrossRefPubMedGoogle Scholar
  64. 64.
    Mann B, Gelos M, Siedow A, Hanski ML, Gratchev A, Ilyas M, Bodmer WF, Moyer MP, Riecken EO, Buhr HJ, Hanski C (1999) Target genes of beta-catenin-T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas. Proc Natl Acad Sci USA 96:1603–1608CrossRefPubMedGoogle Scholar
  65. 65.
    Polakis P (2000) Wnt signaling and cancer. Genes Dev 14:1837–1851PubMedGoogle Scholar
  66. 66.
    Giles RH, van Es JH, Clevers H (2003) Caught up in a Wnt storm: Wnt signaling in cancer. Biochim Biophys Acta 1653:1–24PubMedGoogle Scholar
  67. 67.
    Behrens J (2000) Control of beta-catenin signaling in tumor development. Ann NY Acad Sci 910:21–33PubMedGoogle Scholar
  68. 68.
    Fearnhead NS, Britton MP, Bodmer WF (2001) The ABC of APC. Hum Mol Genet 10:721–733CrossRefPubMedGoogle Scholar
  69. 69.
    Esteller M, Sparks A, Toyota M, Sanchez-Cespedes M, Capella G, Peinado MA, Gonzalez S, Tarafa G, Sidransky D, Meltzer SJ, Baylin SB, Herman JG (2000) Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer. Cancer Res 60:4366–4371PubMedGoogle Scholar
  70. 70.
    Clements WM, Wang J, Sarnaik A, Kim OJ, MacDonald J, Fenoglio-Preiser C, Groden J, Lowy AM (2002) beta-Catenin mutation is a frequent cause of Wnt pathway activation in gastric cancer. Cancer Res 62:3503–3506PubMedGoogle Scholar
  71. 71.
    Gross-Goupil M, Riou P, Emile JF, Saffroy R, Azoulay D, Lacherade I, Receveur A, Piatier-Tonneau D, Castaing D, Debuire B, Lemoine A (2003) Analysis of chromosomal instability in pulmonary or liver metastases and matched primary hepatocellular carcinoma after orthotopic liver transplantation. Int J Cancer 104:745–751CrossRefPubMedGoogle Scholar
  72. 72.
    Wong CM, Fan ST, Ng IO (2001) beta-Catenin mutation and overexpression in hepatocellular carcinoma: clinicopathologic and prognostic significance. Cancer 92:136–145CrossRefPubMedGoogle Scholar
  73. 73.
    Cui J, Zhou X, Liu Y, Tang Z, Romeih M (2003) Wnt signaling in hepatocellular carcinoma: analysis of mutation and expression of beta-catenin, T-cell factor-4 and glycogen synthase kinase 3-beta genes. J Gastroenterol Hepatol 18:280–287CrossRefPubMedGoogle Scholar
  74. 74.
    Harada N, Miyoshi H, Murai N, Oshima H, Tamai Y, Oshima M, Taketo MM (2002) Lack of tumorigenesis in the mouse liver after adenovirus-mediated expression of a dominant stable mutant of beta-catenin. Cancer Res 62:1971–1977PubMedGoogle Scholar
  75. 75.
    Buendia MA (2002) Genetic alterations in hepatoblastoma and hepatocellular carcinoma: common and distinctive aspects. Med Pediatr Oncol 39:530–535CrossRefPubMedGoogle Scholar
  76. 76.
    Ueta T, Ikeguchi M, Hirooka Y, Kaibara N, Terada T (2002) Beta-catenin and cyclin D1 expression in human hepatocellular carcinoma. Oncol Rep 9:1197–1203PubMedGoogle Scholar
  77. 77.
    Edamoto Y, Hara A, Biernat W, Terracciano L, Cathomas G, Riehle HM, Matsuda M, Fujii H, Scoazec JY, Ohgaki H (2003) Alterations of RB1, p53 and Wnt pathways in hepatocellular carcinomas associated with hepatitis C, hepatitis B and alcoholic liver cirrhosis. Int J Cancer 106:334–341CrossRefPubMedGoogle Scholar
  78. 78.
    Huang H, Fujii H, Sankila A, Mahler-Araujo BM, Matsuda M, Cathomas G, Ohgaki H (1999) Beta-catenin mutations are frequent in human hepatocellular carcinomas associated with hepatitis C virus infection. Am J Pathol 155:1795–1801Google Scholar
  79. 79.
    Moreno-Bueno G, Hardisson D, Sanchez C, Sarrio D, Cassia R, Garcia-Rostan G, Prat J, Guo M, Herman JG, Matias-Guiu X, Esteller M, Palacios J (2002) Abnormalities of the APC/beta-catenin pathway in endometrial cancer. Oncogene 21:7981–7990CrossRefPubMedGoogle Scholar
  80. 80.
    Maiti S, Alam R, Amos CI, Huff V (2000) Frequent association of beta-catenin and WT1 mutations in Wilms tumors. Cancer Res 60:6288–6292PubMedGoogle Scholar
  81. 81.
    Koesters R, Niggli F, von Knebel Doeberitz M, Stallmach T (2003) Nuclear accumulation of beta-catenin protein in Wilms’ tumours. J Pathol 199:68–76CrossRefPubMedGoogle Scholar
  82. 82.
    Chesire DR, Ewing CM, Sauvageot J, Bova GS, Isaacs WB (2000) Detection and analysis of beta-catenin mutations in prostate cancer. Prostate 45:323–334CrossRefPubMedGoogle Scholar
  83. 83.
    Gerstein AV, Almeida TA, Zhao G, Chess E, Shih Ie M, Buhler K, Pienta K, Rubin MA, Vessella R, Papadopoulos N (2002) APC/CTNNB1 (beta-catenin) pathway alterations in human prostate cancers. Genes Chromosomes Cancer 34:9–16CrossRefPubMedGoogle Scholar
  84. 84.
    Voeller HJ, Truica CI, Gelmann EP (1998) Beta-catenin mutations in human prostate cancer. Cancer Res 58:2520–2523PubMedGoogle Scholar
  85. 85.
    Schlosshauer PW, Ellenson LH, Soslow RA (2002) Beta-catenin and E-cadherin expression patterns in high-grade endometrial carcinoma are associated with histological subtype. Mod Pathol 15:1032–1037PubMedGoogle Scholar
  86. 86.
    Saegusa M, Okayasu I (2001) Frequent nuclear beta-catenin accumulation and associated mutations in endometrioid-type endometrial and ovarian carcinomas with squamous differentiation. J Pathol 194:59–67CrossRefPubMedGoogle Scholar
  87. 87.
    Shiina H, Igawa M, Shigeno K, Terashima M, Deguchi M, Yamanaka M, Ribeiro-Filho L, Kane CJ, Dahiya R (2002) Beta-catenin mutations correlate with over expression of c-myc and cyclin D1 genes in bladder cancer. J Urol 168:2220–2226CrossRefPubMedGoogle Scholar
  88. 88.
    Rashid A, Gao YT, Bhakta S, Shen MC, Wang BS, Deng J, Fraumeni JF, Jr., Hsing AW (2001) Beta-catenin mutations in biliary tract cancers: a population-based study in China. Cancer Res 61:3406–3409PubMedGoogle Scholar
  89. 89.
    Hoshida Y, Hongyo T, Nakatsuka S, Nishiu M, Takakuwa T, Tomita Y, Nomura T, Aozasa K (2002) Gene mutations in lymphoproliferative disorders of T and NK/T cell phenotypes developing in renal transplant patients. Lab Invest 82:257–264PubMedGoogle Scholar
  90. 90.
    Demunter A, Libbrecht L, Degreef H, De Wolf-Peeters C, van den Oord JJ (2002) Loss of membranous expression of beta-catenin is associated with tumor progression in cutaneous melanoma and rarely caused by exon 3 mutations. Mod Pathol 15:454–461PubMedGoogle Scholar
  91. 91.
    Hsu HC, Jeng YM, Mao TL, Chu JS, Lai PL, Peng SY (2000) Beta-catenin mutations are associated with a subset of low-stage hepatocellular carcinoma negative for hepatitis B virus and with favorable prognosis. Am J Pathol 157:763–770PubMedGoogle Scholar
  92. 92.
    Buendia MA (2000) Genetics of hepatocellular carcinoma. Semin Cancer Biol 10:185–200CrossRefPubMedGoogle Scholar
  93. 93.
    Kolligs FT, Bommer G, Goke B (2002) Wnt/beta-catenin/tcf signaling: a critical pathway in gastrointestinal tumorigenesis. Digestion 66:131–144CrossRefPubMedGoogle Scholar
  94. 94.
    Satoh S, Daigo Y, Furukawa Y, Kato T, Miwa N, Nishiwaki T, Kawasoe T, Ishiguro H, Fujita M, Tokino T, Sasaki Y, Imaoka S, Murata M, Shimano T, Yamaoka Y, Nakamura Y (2000) AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1. Nat Genet 24:245–250PubMedGoogle Scholar
  95. 95.
    Webster MT, Rozycka M, Sara E, Davis E, Smalley M, Young N, Dale TC, Wooster R (2000) Sequence variants of the axin gene in breast, colon, and other cancers: an analysis of mutations that interfere with GSK3 binding. Genes Chromosomes Cancer 28:443–453CrossRefPubMedGoogle Scholar
  96. 96.
    Dahmen RP, Koch A, Denkhaus D, Tonn JC, Sorensen N, Berthold F, Behrens J, Birchmeier W, Wiestler OD, Pietsch T (2001) Deletions of AXIN1, a component of the WNT/wingless pathway, in sporadic medulloblastomas. Cancer Res 61:7039–7043PubMedGoogle Scholar
  97. 97.
    Yokota N, Nishizawa S, Ohta S, Date H, Sugimura H, Namba H, Maekawa M (2002) Role of Wnt pathway in medulloblastoma oncogenesis. Int J Cancer 101:198–201CrossRefPubMedGoogle Scholar
  98. 98.
    Lustig B, Jerchow B, Sachs M, Weiler S, Pietsch T, Karsten U, van de Wetering M, Clevers H, Schlag PM, Birchmeier W, Behrens J (2002) Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors. Mol Cell Biol 22:1184–1193CrossRefPubMedGoogle Scholar
  99. 99.
    Liu W, Dong X, Mai M, Seelan RS, Taniguchi K, Krishnadath KK, Halling KC, Cunningham JM, Boardman LA, Qian C, Christensen E, Schmidt SS, Roche PC, Smith DI, Thibodeau SN (2000) Mutations in AXIN2 cause colorectal cancer with defective mismatch repair by activating beta-catenin/TCF signalling. Nat Genet 26:146–147CrossRefPubMedGoogle Scholar
  100. 100.
    Okino K, Nagai H, Hatta M, Nagahata T, Yoneyama K, Ohta Y, Jin E, Kawanami O, Araki T, Emi M (2003) Up-regulation and overproduction of DVL-1, the human counterpart of the Drosophila dishevelled gene, in cervical squamous cell carcinoma. Oncol Rep 10:1219–1223PubMedGoogle Scholar
  101. 101.
    Uematsu K, He B, You L, Xu Z, McCormick F, Jablons DM (2003) Activation of the Wnt pathway in non small cell lung cancer: evidence of dishevelled overexpression. Oncogene 22:7218–7221CrossRefPubMedGoogle Scholar
  102. 102.
    Uematsu K, Kanazawa S, You L, He B, Xu Z, Li K, Peterlin BM, McCormick F, Jablons DM (2003) Wnt pathway activation in mesothelioma: evidence of Dishevelled overexpression and transcriptional activity of beta-catenin. Cancer Res 63:4547–4551PubMedGoogle Scholar
  103. 103.
    Brown AM (2001) Wnt signaling in breast cancer: have we come full circle? Breast Cancer Res 3:351–355CrossRefPubMedGoogle Scholar
  104. 104.
    Ryo A, Nakamura M, Wulf G, Liou YC, Lu KP (2001) Pin1 regulates turnover and subcellular localization of beta-catenin by inhibiting its interaction with APC. Nat Cell Biol 3:793–801CrossRefPubMedGoogle Scholar
  105. 105.
    Goto H, Kawano K, Kobayashi I, Sakai H, Yanagisawa S (2002) Expression of cyclin D1 and GSK-3beta and their predictive value of prognosis in squamous cell carcinomas of the tongue. Oral Oncol 38:549–556CrossRefPubMedGoogle Scholar
  106. 106.
    Bijur GN, Jope RS (2001) Proapoptotic stimuli induce nuclear accumulation of glycogen synthase kinase-3 beta. J Biol Chem 276:37436–37442CrossRefPubMedGoogle Scholar
  107. 107.
    Diehl JA, Cheng M, Roussel MF, Sherr CJ (1998) Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization. Genes Dev 12:3499–3511PubMedGoogle Scholar
  108. 108.
    Franca-Koh J, Yeo M, Fraser E, Young N, Dale TC (2002) The regulation of glycogen synthase kinase-3 nuclear export by Frat/GBP. J Biol Chem 277:43844–43848CrossRefPubMedGoogle Scholar
  109. 109.
    Thomas GM, Frame S, Goedert M, Nathke I, Polakis P, Cohen P (1999) A GSK3-binding peptide from FRAT1 selectively inhibits the GSK3-catalysed phosphorylation of axin and beta-catenin. FEBS Lett 458:247–251CrossRefPubMedGoogle Scholar
  110. 110.
    Fraser E, Young N, Dajani R, Franca-Koh J, Ryves J, Williams RS, Yeo M, Webster MT, Richardson C, Smalley MJ, Pearl LH, Harwood A, Dale TC (2002) Identification of the axin and Frat binding region of glycogen synthase kinase-3. J Biol Chem 277:2176–2185CrossRefPubMedGoogle Scholar
  111. 111.
    Ferkey DM, Kimelman D (2002) Glycogen synthase kinase-3 beta mutagenesis identifies a common binding domain for GBP and axin. J Biol Chem 277:16147–16152CrossRefPubMedGoogle Scholar
  112. 112.
    ter Haar E, Coll JT, Austen DA, Hsiao HM, Swenson L, Jain J (2001) Structure of GSK3beta reveals a primed phosphorylation mechanism. Nat Struct Biol 8:593–596CrossRefPubMedGoogle Scholar
  113. 113.
    Dajani R, Fraser E, Roe SM, Yeo M, Good VM, Thompson V, Dale TC, Pearl LH (2003) Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex. EMBO J 22:494–501CrossRefPubMedGoogle Scholar
  114. 114.
    Dajani R, Fraser E, Roe SM, Young N, Good V, Dale TC, Pearl LH (2001) Crystal structure of glycogen synthase kinase 3 beta: structural basis for phosphate-primed substrate specificity and autoinhibition. Cell 105:721–732CrossRefPubMedGoogle Scholar
  115. 115.
    Bax B, Carter PS, Lewis C, Guy AR, Bridges A, Tanner R, Pettman G, Mannix C, Culbert AA, Brown MJ, Smith DG, Reith AD (2001) The structure of phosphorylated GSK-3beta complexed with a peptide, FRATtide, that inhibits beta-catenin phosphorylation. Structure (Camb) 9:1143–1152Google Scholar
  116. 116.
    Watcharasit P, Bijur GN, Zmijewski JW, Song L, Zmijewska A, Chen X, Johnson GV, Jope RS (2002) Direct, activating interaction between glycogen synthase kinase-3beta and p53 after DNA damage. Proc Natl Acad Sci USA 99:7951–7955CrossRefPubMedGoogle Scholar
  117. 117.
    Watcharasit P, Bijur GN, Song L, Zhu J, Chen X, Jope RS (2003) Glycogen synthase kinase-3b (GSK3b) binds to, and promotes the actions of, p53. J Biol Chem 278:48872–48879CrossRefPubMedGoogle Scholar
  118. 118.
    Grimes CA, Jope RS (2001) CREB DNA binding activity is inhibited by glycogen synthase kinase-3 beta and facilitated by lithium. J Neurochem 78:1219–1232CrossRefPubMedGoogle Scholar
  119. 119.
    Watanabe T, Sugaya M, Atkins AM, Aquilino EA, Yang A, Borris DL, Brady J, Blauvelt A (2003) Kaposi’s sarcoma-associated herpesvirus latency-associated nuclear antigen prolongs the life span of primary human umbilical vein endothelial cells. J Virol 77:6188–6196CrossRefPubMedGoogle Scholar
  120. 120.
    Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K, Hintz L, Nusse R, Weissman IL (2003) A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 423:409–414CrossRefPubMedGoogle Scholar
  121. 121.
    Wang X, Xiao Y, Mou Y, Zhao Y, Blankesteijn WM, Hall JL (2002) A role for the beta-catenin/T-cell factor signaling cascade in vascular remodeling. Circ Res 90:340–347CrossRefPubMedGoogle Scholar
  122. 122.
    Wright M, Aikawa M, Szeto W, Papkoff J (1999) Identification of a Wnt-responsive signal transduction pathway in primary endothelial cells. Biochem Biophys Res Commun 263:384–388CrossRefPubMedGoogle Scholar
  123. 123.
    Cohen P, Frame S (2001) The renaissance of GSK3. Nat Rev Mol Cell Biol 2:769–776CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Viral Oncology Program, Sidney Kimmel Cancer CenterJohns Hopkins School of MedicineBaltimoreUSA
  2. 2.The Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins School of MedicineBaltimoreUSA

Personalised recommendations