Secretory Clusterin Is a Marker of Tumor Progression Regulated by IGF-1 and Wnt Signaling Pathways

  • Yonglong Zou
  • Eva M. Goetz
  • Masatoshi Suzuki
  • David A. Boothman
Conference paper

Abstract

Secretory clusterin (sCLU) is a pro-survival factor that can be induced by cellular stress, including ionizing radiation (IR), many cytotoxic agents, and during cellular replicative or low doses of stress-induced senescence. sCLU expression changes with tumor stage and grade in various types of cancer. Previously our laboratory found that sCLU was induced by IR through activation of the IGF-1R/Src/MEK/ Erk/Egr-1 pathway. APC loss in Min-/-?mice was also linked to elevated sCLU expression, especially in human colon cancer. We now fi nd that Wnt signaling can cross talk with IGF-1 signaling to regulate sCLU expression. The cross talk between the IGF-1 and Wnt signaling pathways is very complex, not only because they share many components but also because they are delicately regulated by time, dose, and cell type. Both positive and negative feedback regulation loops regulate sCLU expression. Understanding these complicated signaling pathways will be essential for delineating the roles of Wnt, IGF-1, and sCLU expression in tumor progression, aging, and cancer, as well as in heart and Alzheimer’s diseases aberrant where sCLU expression has been implicated.

Key words

Clusterin IGF-1 Wnt TGF-β1 GSK3β β-catenin TCF APC Egr-1 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Criswell T, Beman M, Araki S, et al (2005) Delayed activation of insulin-like growth factor-1 receptor/Src/MAPK/Egr-1 signaling regulates clusterin expression, a pro-survival factor. J Biol Chem 280:14212–14221PubMedCrossRefGoogle Scholar
  2. 2.
    Pucci S, Bonanno E, Pichiorri F, et al (2004) Modulation of different clusterin isoforms in human colon tumorigenesis. Oncogene 23:2298–2304PubMedCrossRefGoogle Scholar
  3. 3.
    Krijnen PAJ, Cillessen SAGM, Manoe R, et al (2005) Clusterin: a protective mediator for ischemic cardiomyocytes? Am J Physiol Heart Circ Physiol 289:H2193–H2202PubMedCrossRefGoogle Scholar
  4. 4.
    Shannan B, Seifert M, Leskov K, et al (2006) Challenge and promise: roles for clusterin in pathogenesis, progression and therapy of cancer. Cell Death Differ 13:12–19PubMedCrossRefGoogle Scholar
  5. 5.
    x M, Goetz EC, Venezianoa G, et al (2007) Secretory clusterin (sCLU) is a hallmark sensor of DNA damage, cell stress, and cellular senescence: evidence for similar regulation of sCLU expression after cellular stress and replicative senescence. Radiation Risk Perspectives: Proceedings of the Second Nagasaki Symposium of International Consortium for Medical Care of Hibakusha and Radiation Life Science 1299:150–157Google Scholar
  6. 6.
    Trougakos IP, Pawelec G, Tzavelas C, et al (2006) Clusterin/Apolipoprotein J up-regulation after zinc exposure, replicative senescence or differentiation of human haematopoietic cells. Biogerontology 7:375–382PubMedCrossRefGoogle Scholar
  7. 7.
    Criswell T, Klokov D, Beman M, et al (2003) Repression of IR-inducible clusterin expression by the p53 tumor suppressor protein. Cancer Biol Ther 2:372–380PubMedGoogle Scholar
  8. 8.
    Ashcroft M, Ludwig RL, Woods DB, et al (2002) Phosphorylation of HDM2 by Akt. Oncogene 21:1955–1962PubMedCrossRefGoogle Scholar
  9. 9.
    Ishikawa Y (2005) Wnt signaling and orthopedic diseases. Am J Pathol 167:1–3PubMedGoogle Scholar
  10. 10.
    Chen X, Halberg RB, Ehrhardt WM, et al (2003) Clusterin as a biomarker in murine and human intestinal neoplasia. Proc Natl Acad Sci U S A 100:9530–9535PubMedCrossRefGoogle Scholar
  11. 11.
    van Weeren PC, de Bruyn KM, de Vries-Smits AM, et al (1998) Essential role for protein kinase B (PKB) in insulin-induced glycogen synthase kinase 3 inactivation. Characterization of dominant-negative mutant of PKB. J Biol Chem 273:13150–13156PubMedCrossRefGoogle Scholar
  12. 12.
    Rubinfeld B, Albert I, Porfiri E, et al (1996) Binding of GSK3β to the APC-β-catenin complex and regulation of complex assembly. Science 272:1023–1026PubMedCrossRefGoogle Scholar
  13. 13.
    Hart MJ, de los Santos R, Albert IN, et al (1998) Downregulation of β-catenin by human Axin and its association with the APC tumor suppressor, β-catenin and GSK3 β. Curr Biol 8:573–581PubMedCrossRefGoogle Scholar
  14. 14.
    Lee E, Salic A, Kirschner MW (2001) Physiological regulation of α-catenin stability by TCF3 and CK1epsilon. J Cell Biol 154:983–993PubMedCrossRefGoogle Scholar
  15. 15.
    Staal FJT, Burgering BT, van de Wetering M, et al (1999) TCF-1 mediated transcription in T lymphocytes: differential role for glycogen synthase kinase-3 in fibroblasts and T cells. Int Immunol 11:312–317CrossRefGoogle Scholar
  16. 16.
    Yuan H, Mao J, Li L, et al (1999) Suppression of glycogen synthase kinase activity is not suffi cient for leukemia enhancer factor 1 activation. J Biol Chem 274:30419–30423PubMedCrossRefGoogle Scholar
  17. 17.
    Christèle D, Axelle C, Marie-José B, et al (2001) Insulin and IGF-1 stimulate the bold-catenin pathway through two signalling cascades involving GSK-3β inhibition and Ras activation. Oncogene 20:252–259CrossRefGoogle Scholar
  18. 18.
    Li L, Yuan H, Weaver CD, et al (1999) Axin and Frat1 interact with dvl and GSK, bridging Dvl to GSK in Wnt-mediated regulation of LEF-1. EMBO J 18:4233–4240PubMedCrossRefGoogle Scholar
  19. 19.
    Yost C, Farr G, Pierce SB, et al (1998) GBP, an inhibitor of GSK-3, is implicated in Xenopus development and oncogenesis. Cell 93:1031–1041PubMedCrossRefGoogle Scholar
  20. 20.
    Polakis P (2000) Wnt signaling and cancer. Genes Dev 14:1837–1851PubMedGoogle Scholar
  21. 21.
    Harwood AJ (2001) Regulation of GSK-3 a cellular multiprocessor. Cell 105:821–824PubMedCrossRefGoogle Scholar
  22. 22.
    Amit S, Hatzubai A, Birman Y, et al (2002) Axin-mediated CKI phosphorylation of β-catenin at Ser 45: a molecular switch for the Wnt pathway. Genes Dev 16:1066–1076PubMedCrossRefGoogle Scholar
  23. 23.
    Salic A, Lee E, Mayer L, et al (2000) Control of β-catenin stability: reconstitution of the cytoplasmic steps of the wnt pathway in Xenopus egg extracts. Mol Cell 5:523–532PubMedCrossRefGoogle Scholar
  24. 24.
    Farr GH, Ferkey DM, Yost C, et al (2000) Interaction among GSK-3, GBP, axin, and APC in Xenopus axis specification. J Cell Biol 148:691–702PubMedCrossRefGoogle Scholar
  25. 25.
    Ding VW, Chen RH, McCormick F (2000) Differential regulation of glycogen synthase kinase 3α?by insulin and Wnt signaling. J Biol Chem 275:32475–32481PubMedCrossRefGoogle Scholar
  26. 26.
    Chen RH, Ding WV, McCormick F (2000) Wnt signaling to beta-catenin involves two interactive components. Glycogen synthase kinase-3beta inhibition and activation of protein kinase C. J Biol Chem 275:17894–17899PubMedCrossRefGoogle Scholar
  27. 27.
    Fukumoto S, Hsieh CM, Maemura K, et al (2001) Akt participation in the Wnt signaling pathway through Dishevelled. J Biol Chem 276:17479–17483PubMedCrossRefGoogle Scholar
  28. 28.
    Fidler IJ (2003) The pathogenesis of cancer metastasis: the “seed and soil” hypothesis revisited. Nat Rev Cancer 3:453–458PubMedCrossRefGoogle Scholar
  29. 29.
    Leader M, Collins M, Patel J, et al (1987) Vimentin: an evaluation of its role as a tumour marker. Histopathology (Oxf) 11:63–72Google Scholar
  30. 30.
    Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2:442–454PubMedCrossRefGoogle Scholar
  31. 31.
    Shook D, Keller R (2003) Mechanisms, mechanics and function of epithelial-mesenchymal transitions in early development. Mech Dev 120:1351–1383PubMedCrossRefGoogle Scholar
  32. 32.
    Morali OG, Delmas V, Moore R, et al (2001) IGF-II induces rapid β-catenin relocation to the nucleus during epithelium to mesenchyme transition. Oncogene 20:4942–4950PubMedCrossRefGoogle Scholar
  33. 33.
    Vecchione A, Marchese A, Henry P, et al (2003) The Grb10/Nedd4 complex regulates ligandinduced ubiquitination and stability of the insulin-like growth factor I receptor. Mol Cell Biol 23:3363–3372PubMedCrossRefGoogle Scholar
  34. 34.
    Girnita L, Girnita A, Larsson O (2003) Mdm2-dependent ubiquitination and degradation of the insulin-like growth factor 1 receptor. Proc Natl Acad Sci U S A 100:8247–8252PubMedCrossRefGoogle Scholar
  35. 35.
    Avizienyte E, Wyke AW, Jones RJ, et al (2002) Src-induced de-regulation of E-cadherin in colon cancer cells requires integrin signalling. Nat Cell Biol 4:632–638PubMedGoogle Scholar
  36. 36.
    Graham TA, Weaver C, Mao F, et al (2000) Crystal structure of a β-catenin/TCF complex. Cell 103:885–896PubMedCrossRefGoogle Scholar
  37. 37.
    Grille SJ, Bellacosa A, Upson J, et al (2003) The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res 63:2172–2178PubMedGoogle Scholar
  38. 38.
    Jian H, Shen X, Liu I, et al (2006) Smad3-dependent nuclear translocation of β-catenin is required for TGF-β1-induced proliferation of bone marrow-derived adult human mesenchymal stem cells. Genes Dev 20:666–674PubMedCrossRefGoogle Scholar
  39. 39.
    Palacios F, Tushir JS, Fujita Y, et al (2005) Lysosomal targeting of E-cadherin: a unique mechanism for the down-regulation of cell-cell adhesion during epithelial to mesenchymal transitions. Mol Cell Biol 25:389–402PubMedCrossRefGoogle Scholar
  40. 40.
    Julien S, Puig I, Caretti E, et al (2007) Activation of NF-kappaB by Akt upregulates Snail expression and induces epithelium mesenchyme transition. Oncogene 26:7445–7456PubMedCrossRefGoogle Scholar
  41. 41.
    Chua HL, Bhat-Nakshatri P, Clare SE, et al (2007) NF-kappaB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells: potential involvement of ZEB-1 and ZEB-2. Oncogene 26:711–724PubMedCrossRefGoogle Scholar
  42. 42.
    Bachelder RE, Yoon SO, Franci C, et al (2005) Glycogen synthase kinase-3 is an endogenous inhibitor of Snail transcription: implications for the epithelial-mesenchymal transition. J Cell Biol 168:29–33PubMedCrossRefGoogle Scholar
  43. 43.
    Reddy P, Liu L, Ren C, et al (2005) Formation of E-cadherin-mediated cell-cell adhesion activates AKT and mitogen activated protein kinase via phosphatidylinositol 3 kinase and ligand-independent activation of epidermal growth factor receptor in ovarian cancer cells. Mol Endocrinol 19:2564–2578PubMedCrossRefGoogle Scholar
  44. 44.
    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
  45. 45.
    Jin G, Howe HP (1997) Regulation of clusterin gene expression by transforming growth factor β. J Biol Chem 272:26620–26626PubMedCrossRefGoogle Scholar
  46. 46.
    Reddy KB, Karode MC, Harmony AK, et al (1996) Interaction of transforming growth factor β?receptors with apolipoprotein J/clusterin. Biochemistry 35:309–314PubMedCrossRefGoogle Scholar
  47. 47.
    Guo X, Ramirez A, Waddell DS, et al (2008) Axin and GSK3-β control Smad3 protein stability and modulate TGF-signaling. Genes Dev 22:106–120PubMedCrossRefGoogle Scholar
  48. 48.
    Marcopoulou CE, Vavouraki HN, Dereka XE, et al (2003) Proliferative effect of growth factors TGF-β1, PDGF-BB and rhBMP-2 on human gingival fibroblasts and periodontal ligament cells. J Int Acad Periodontol 5:63–70PubMedGoogle Scholar
  49. 49.
    Yan Z, Deng X, Friedman E (2001) Oncogenic Ki-ras confers a more aggressive colon cancer phenotype through modifi cation of transforming growth factor-β receptor III. J Biol Chem 276:1555–1563PubMedCrossRefGoogle Scholar
  50. 50.
    Wegrowski Y, Perreau C, Martiny L, et al (1997) Transforming growth factor β-1 up-regulates clusterin synthesis in thyroid epithelial cells. Exp Cell Res 247:475–483CrossRefGoogle Scholar

Copyright information

© Springer 2009

Authors and Affiliations

  • Yonglong Zou
    • 1
  • Eva M. Goetz
    • 1
  • Masatoshi Suzuki
    • 1
  • David A. Boothman
    • 1
  1. 1.Laboratory of Molecular Stress Responses, Program in Cell Stress and Cancer Nanomedicine, Department of Oncology, Simmons Comprehensive Cancer CenterUniversity of Texas Southwestern Medical Center at DallasND 2.210kUSA

Personalised recommendations