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The Role of Insulin-Like Growth Factors in the Epithelial to Mesenchymal Transition

  • Chapter
Rise and Fall of Epithelial Phenotype

Abstract

IGFs (insulin-like growth factors) are peptides known to stimulate a wide range of actions on different tissues. Indeed, IGFs can stimulate anabolism, acute metabolic effects as well as enhancing more chronic effects such as cell proliferation and differentiation together with protecting cells from apoptosis. Recently, it was shown that IGFs induce an epithelial to mesenchymal transition (EMT), a crucial morphogenic event during development and transformation. Here, the cellular and molecular aspects of IGF-induced EMT are reviewed. Major signaling pathways downstream of IGFs are described in order to introduce molecules that are believed to convey the EMT signal. The roles and targets of these molecules are analysed. The importance of IGFs in cellular events which when dysregulated lead to neoplasia is discussed in this review.

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References

  1. Ron G, Roscnfeld CTR. The IGF system. Totowa, New Jersey: Humana Press, 1999.

    Google Scholar 

  2. Toyoshima K, Ito N, Hiasa Y et al. Tissue culture of urinary bladder tumor induced in a rat by N-butyl-N-(-4-hydroxybutyl)nitrosamine: Establishment of cell line, Nara Bladder Tumor II. J Natl Cancer Inst 1971;47(5):979–985.

    PubMed  CAS  Google Scholar 

  3. Morali OG, Delmas V, Moore R et al. IGF-II induces rapid beta-catenin relocation to the nucleus during epithelium to mesenchyme transition. Oncogene 2001;20(36):4942–4950.

    PubMed  CAS  Google Scholar 

  4. Valles AM, Boyer B, Badet J et al. Acidic fibroblast growth factor is a modulator of epithelial plasticity in a rat bladder carcinoma cell line. Proc Natl Acad Sci USA 1990;87(3):1124–1128.

    PubMed  CAS  Google Scholar 

  5. Gavrilovic J, Moens G, Thiery JP et al. Expression of transfected transforming growth factor alpha induces a motile fibroblast-like phenotype with extracellular matrix-degrading potential in a rat bladder carcinoma cell line. Cell Regul 1990;1(13):1003–1014.

    PubMed  CAS  Google Scholar 

  6. Guvakova MA, Adams JC, Boettiger D. Functional role of alpha-actinin, PI 3-kinase and MEK1/2 in insulin-like growth factor I receptor kinase regulated motility of human breast carcinoma cells. J Cell Sci 2002; 115(Pt 21):4149–4165.

    PubMed  CAS  Google Scholar 

  7. Li Y, Bhargava MM, Joseph A et al. Goldberg ID. Effect of hepatocyte growth factor/scatter factor and other growth factors on motility and morphology of nontumorigenic and tumor cells. In Vitro Cell Dev Biol Anim 1994;30A(2):105–110.

    PubMed  CAS  Google Scholar 

  8. Guvakova MA, Surmacz E. Overexpressed IGF-I receptors reduce estrogen growth requirements, enhance survival, and promote E-cadherin-mediated cell-cell adhesion in human breast cancer cells. Exp Cell Res 1997;231(1):149–162.

    PubMed  CAS  Google Scholar 

  9. Bauer A, Lickert H, Kemler R et al. Modification of the E-cadherin-catenin complex in mitotic Madin-Darby canine kidney epithelial cells. J Biol Chem 1998; 273(43):28314–28321.

    PubMed  CAS  Google Scholar 

  10. Le TL, Yap AS, Stow JL. Recycling of E-cadherin: A potential mechanism for regulating cadherin dynamics. J Cell Biol 1999;146(1):219–232.

    PubMed  CAS  Google Scholar 

  11. Butz S, Larue L. Expression of catenins during mouse embryonic development and in adult tissues. Cell Adhes Commun 1995;3(4):337–352.

    PubMed  CAS  Google Scholar 

  12. Yost C, Torres M, Miller JR et al. The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3. Genes Dev 1996;10(12):1443–1454.

    PubMed  CAS  Google Scholar 

  13. Aberle H, Bauer A, Stappert J et al. Beta-catenin is a target for the ubiquitin-proteasome pathway. Embo J 1997;16(13):3797–3804.

    PubMed  CAS  Google Scholar 

  14. Axelrod JD, Miller JR, Shulman JM et al. Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways. Genes Dev 1998;12(16):2610–2622.

    PubMed  CAS  Google Scholar 

  15. Yanagawa S, van Leeuwen F, Wodarz A et al. The dishevelled protein is modified by wingless signaling in Drosophila. Genes Dev 1995;9(9):1087–1097.

    PubMed  CAS  Google Scholar 

  16. Karasawa T, Yokokura H, Kitajewski J et al. Frizzled-9 is activated by Wnt-2 and functions in Wnt/beta-catenin signaling. J Biol Chem 2002;277(40):37479–37486.

    PubMed  CAS  Google Scholar 

  17. Novak A, Dedhar S. Signaling through beta-catenin and Lef/Tcf. Cell Mol Life Sci 1999;56(5–6):523–537.

    PubMed  CAS  Google Scholar 

  18. Shtutman M, Zhurinsky J, Simcha I et al. The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Natl Acad Sci USA 1999;96(10):5522–5527.

    PubMed  CAS  Google Scholar 

  19. He TC, Sparks AB, Rago C et al. Identification of c-MYC as a target of the APC pathway. Science 1998;281(5382):1509–1512.

    PubMed  CAS  Google Scholar 

  20. Mann B, Gelos M, Siedow A et al. Target genes of beta-catenin-T cell-factor/lymphoidenhancer-factor signaling in human colorectal carcinomas. Proc Natl Acad Sci USA 1999;96(4):1603–1608.

    PubMed  CAS  Google Scholar 

  21. Arnold SJ, Stappert J, Bauer A et al. Brachyury is a target gene of the Wnt/beta-catenin signaling pathway. Mech Dev 2000;91(1–2):249–258.

    PubMed  CAS  Google Scholar 

  22. Brabletz T, Jung A, Dag S et al. Beta-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer. Am J Pathol 1999;155(4):1033–1038.

    PubMed  CAS  Google Scholar 

  23. Crawford HC, Fingleton BM, Rudolph-Owen LA et al. The metalloproteinase matrilysin is a target of beta-catenin transactivation in intestinal tumors. Oncogene 1999;18(18):2883–2891.

    PubMed  CAS  Google Scholar 

  24. Gradl D, Kuhl M, Wedlich D. The Wnt/Wg signal transducer beta-catenin controls fibronectin expression. Mol Cell Biol 1999;19(8):5576–5587.

    PubMed  CAS  Google Scholar 

  25. Howe LR, Subbaramaiah K, Chung WJ et al. Transcriptional activation of cyclooxygenase-2 in Wnt-1-transformed mouse mammary epithelial cells. Cancer Res 1999;59(7):1572–1577.

    PubMed  CAS  Google Scholar 

  26. Takeda K, Yasumoto K, Takada R et al. Induction of melanocyte-specific microphthalmia-associated transcription factor by Wnt-3a. J Biol Chem 2000;275(19):14013–14016.

    PubMed  CAS  Google Scholar 

  27. Batlle E, Henderson JT, Beghtel H et al. Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell 2002;111(2):251–263.

    PubMed  CAS  Google Scholar 

  28. Fuse N, Yasumoto K, Takeda K et al. Molecular cloning of cDNA encoding a novel microphthalmia-associated transcription factor isoform with a distinct amino-terminus. J Biochem (Tokyo) 1999;126(6):1043–1051.

    PubMed  CAS  Google Scholar 

  29. Amae S, Fuse N, Yasumoto K et al. Identification of a novel isoform of microphthalmia-associated transcription factor that is enriched in retinal pigment epithelium. Biochem Biophys Res Commun 1998;247(3):710–715.

    PubMed  CAS  Google Scholar 

  30. Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 2000;103(2):211–225.

    PubMed  CAS  Google Scholar 

  31. Favelyukis S, Till JH, Hubbard SR et al. Structure and autoregulation of the insulin-like growth factor 1 receptor kinase. Nat Struct Biol 2001;8(12):1058–1063.

    PubMed  CAS  Google Scholar 

  32. Ullrich A, Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell 1990;61(2):203–212.

    PubMed  CAS  Google Scholar 

  33. Dong LQ, Farris S, Christal J et al. Site-directed mutagenesis and yeast two-hybrid studies of the insulin and insulin-like growth factor-1 receptors: The Src homology-2 domain-containing protein hGrb10 binds to the autophosphorylated tyrosine residues in the kinase domain of the insulin receptor. Mol Endocrinol Nov 1997;11(12):1757–1765.

    CAS  Google Scholar 

  34. Dong LQ, Farris S, Christal J et al. Site-directed mutagenesis and yeast two-hybrid studies of the insulin and insulin-like growth factor-1 receptors: The Src homology-2 domain-containing protein hGrb10 binds to the autophosphorylated tyrosine residues in the kinase domain of the insulin receptor. Mol Endocrinol 1997;11(12):1757–1765.

    PubMed  CAS  Google Scholar 

  35. Morrione A, Valentinis B, Resnicoff M et al. The role of mGrb10alpha in insulin-like growth factor I-mediated growth. J Biol Chem 1997;272(42):26382–26387.

    PubMed  CAS  Google Scholar 

  36. Wang J, Dai H, Yousaf N et al. Grb10, a positive, stimulatory signaling adapter in platelet-derived growth factor BB-, insulin-like growth factor I-, and insulin-mediated mitogenesis. Mol Cell Biol 1999;19(9):6217–6228.

    PubMed  CAS  Google Scholar 

  37. Stein EG, Gustafson TA, Hubbard SR. The BPS domain of Grb10 inhibits the catalytic activity of the insulin and IGF1 receptors. FEBS Lett 2001;493(2–3):106–111.

    PubMed  CAS  Google Scholar 

  38. Dey BR, Frick K, Lopaczynski W et al. Evidence for the direct interaction of the insulin-like growth factor I receptor with IRS-1, Shc, and Grb10. Mol Endocrinol 1996;10(6):631–641.

    PubMed  CAS  Google Scholar 

  39. Sasaoka T, Rose DW, Jhun BH et al. Evidence for a functional role of Shc proteins in mitogenic signaling induced by insulin, insulin-like growth factor-1, and epidermal growth factor. J Biol Chem 1994;269(18):13689–13694.

    PubMed  CAS  Google Scholar 

  40. Rozakis-Adcock M, Fernley R, Wade J et al. The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1. Nature 1993;363(6424):83–85.

    PubMed  CAS  Google Scholar 

  41. Lowenstein EJ, Daly RJ, Batzer AG et al. The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell 1992;70(3):431–442.

    PubMed  CAS  Google Scholar 

  42. Matsuda M, Hashimoto Y, Muroya K et al. CRK protein binds to two guanine nucleotide-releasing proteins for the Ras family and modulates nerve growth factor-induced activation of Ras in PC12 cells. Mol Cell Biol 1994;14(8):5495–5500.

    PubMed  CAS  Google Scholar 

  43. Ohba Y, Mochizuki N, Yamashita S et al. Regulatory proteins of R-Ras, TC21/R-Ras2, and M-Ras/R-Ras3. J Biol Chem 2000;275(26):20020–20026.

    PubMed  CAS  Google Scholar 

  44. Gotoh T, Niino Y, Tokuda M et al. Activation of R-Ras by Ras-guanine nucleotide-releasing factor. J Biol Chem 1997;272(30):18602–18607.

    PubMed  CAS  Google Scholar 

  45. Craparo A, O’Neill TJ, Gustafson TA. NonSH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor. J Biol Chem 1995;270(26):15639–15643.

    PubMed  CAS  Google Scholar 

  46. Kuhne MR, Pawson T, Lienhard GE et al. The insulin receptor substrate 1 associates with the SH2-containing phosphotyrosine phosphatase Syp. J Biol Chem 1993;268(16):11479–11481.

    PubMed  CAS  Google Scholar 

  47. Qu CK. The SHP-2 tyrosine phosphatase: Signaling mechanisms and biological functions. Cell Res 2000;10(4):279–288.

    PubMed  CAS  Google Scholar 

  48. Courtneidge SA, Fumagalli S, Koegl M et al. The Src family of protein tyrosine kinases: Regulation and functions. Dev Suppl 1993:57–64.

    Google Scholar 

  49. Tobe K, Sabe H, Yamamoto T et al. Csk enhances insulin-stimulated dephosphorylation of focal adhesion proteins. Mol Cell Biol 1996;16(9):4765–4772.

    PubMed  CAS  Google Scholar 

  50. Li W, Fan J, Woodley DT. Nck/Dock: An adapter between cell surface receptors and the actin cytoskeleton. Oncogene 2001;20(44):6403–6417.

    PubMed  CAS  Google Scholar 

  51. Boney CM, Sekimoto H, Gruppuso PA et al. Src family tyrosine kinases participate in insulin-like growth factor I mitogenic signaling in 3T3-L1 cells. Cell Growth Differ 2001;12(7):379–386.

    PubMed  CAS  Google Scholar 

  52. Mason CS, Springer CJ, Cooper RG et al. Serine and tyrosine phosphorylations cooperate in Raf-1, but not B-Raf activation. Embo J 1999;18(8):2137–2148.

    PubMed  CAS  Google Scholar 

  53. Treisman R. Journey to the surface of the cell: Fos regulation and the SRE. Embo J 1995;14(20):4905–4913.

    PubMed  CAS  Google Scholar 

  54. Herrera R. Modulation of hepatocyte growth factor-induced scattering of HT29 colon carcinoma cells. Involvement of the MAPK pathway. J Cell Sci 1998;111 (Pt 8):1039–1049.

    PubMed  CAS  Google Scholar 

  55. Kodaki T, Woscholski R, Hallberg B et al. The activation of phosphatidylinositol 3-kinase by Ras. Curr Biol 1994;4(9):798–806.

    PubMed  CAS  Google Scholar 

  56. Rodriguez-Viciana P, Warne PH, Vanhaesebroeck B et al. Activation of phosphoinositide 3-kinase by interaction with Ras and by point mutation. Embo J 1996;15(10):2442–2451.

    PubMed  CAS  Google Scholar 

  57. Chan TO, Tsichlis PN. PDK2: A complex tail in one Akt. Sci STKE 2001;2001(66):E1.

    Article  Google Scholar 

  58. Du K, Montminy M. CREB is a regulatory target for the protein kinase Akt/PKB. J Biol Chem 1998;273(49):32377–32379.

    PubMed  CAS  Google Scholar 

  59. Brunet A, Bonni A, Zigmond MJ et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 1999;96(6):857–868.

    PubMed  CAS  Google Scholar 

  60. Tang ED, Nunez G, Barr FG et al. Negative regulation of the forkhead transcription factor FKHR by Akt. J Biol Chem 1999;274(24):16741–16746.

    PubMed  CAS  Google Scholar 

  61. Smith JL, Schaffner AE, Hofmeister JK et al. Ets-2 is a target for an akt (Protein kinase B)/jun N-terminal kinase signaling pathway in macrophages of motheaten-viable mutant mice. Mol Cell Biol 2000;20(21):8026–8034.

    PubMed  CAS  Google Scholar 

  62. Testa JR, Bellacosa A. AKT plays a central role in tumorigenesis. Proc Natl Acad Sci USA 2001;98(20):10983–10985.

    PubMed  CAS  Google Scholar 

  63. Frame MC. Src in cancer: Deregulation and consequences for cell behaviour. Biochim Biophys Acta 2002;1602(2):114–130.

    PubMed  CAS  Google Scholar 

  64. Kaplan KB, Swedlow JR, Varmus HE et al. Association of p60c-src with endosomal membranes in mammalian fibroblasts. J Cell Biol 1992;118(2):321–333.

    PubMed  CAS  Google Scholar 

  65. Fincham VJ, Unlu M, Brunton VG et al. Translocation of Src kinase to the cell periphery is mediated by the actin cytoskeleton under the control of the Rho family of small G proteins. J Cell Biol 1996;135(6 Pt 1):1551–1564.

    PubMed  CAS  Google Scholar 

  66. Fincham VJ, Brunton VG, Frame MC. The SH3 domain directs acto-myosin-dependent targeting of v-Src to focal adhesions via phosphatidylinositol 3-kinase. Mol Cell Biol 2000;20(17):6518–6536.

    PubMed  CAS  Google Scholar 

  67. Bence-Hanulec KK, Marshall J, Blair LA. Potentiation of neuronal L calcium channels by IGF-1 requires phosphorylation of the alpha1 subunit on a specific tyrosine residue. Neuron 2000;27(1):121–131.

    PubMed  CAS  Google Scholar 

  68. Arbet-Engels C, TartareDeckert S, Eckhart W. C-terminal Src kinase associates with ligand-stimulated insulin-like growth factor-I receptor. J Biol Chem 1999;274(9):5422–5428.

    PubMed  CAS  Google Scholar 

  69. Azarnia R, Reddy S, Kmiecik TE et al. The cellular src gene product regulates junctional cell-to-cell communication. Science 1988;239(4838):398–401.

    PubMed  CAS  Google Scholar 

  70. Toyofuku T, Yabuki M, Otsu K et al. Functional role of c-Src in gap junctions of the cardiomyopathic heart. Circ Res 1999;85(8):672–681.

    PubMed  CAS  Google Scholar 

  71. Toyofuku T, Akamatsu Y, Zhang H et al. C-Src regulates the interaction between connexin-43 and ZO-1 in cardiac myocytes. J Biol Chem 2001;276(3):1780–1788.

    PubMed  CAS  Google Scholar 

  72. Rodier JM, Valles AM, Denoyelle M et al. pp60c-src is a positive regulator of growth factor-induced cell scattering in a rat bladder carcinoma cell line. J Cell Biol 1995; 131(3):761–773.

    PubMed  CAS  Google Scholar 

  73. Boyer B, Roche S, Denoyelle M et al. Src and Ras are involved in separate pathways in epithelial cell scattering. Embo J 1997; 16(19):5904–5913.

    PubMed  CAS  Google Scholar 

  74. Volberg T, Geiger B, Dror R et al. Modulation of intercellular adherens-type junctions and tyrosine phosphorylation of their components in RSV-transformed cultured chick lens cells. Cell Regul 1991; 2(2):105–120.

    PubMed  CAS  Google Scholar 

  75. Gomez S, del Mont Llosas M, Verdu J et al. Independent regulation of adherens and tight junctions by tyrosine phosphorylation in Caco2 cells. Biochim Biophys Acta 1999; 1452(2):121–132.

    PubMed  CAS  Google Scholar 

  76. Hansson A, Thoren M. Activation of MAP kinase in Swiss 3T3 fibroblasts by insulin-like growth factor-I. Growth Regul 1995; 5(2):92–100.

    PubMed  CAS  Google Scholar 

  77. Casamassima A, Rozengurt E. Insulin-like growth factor I stimulates tyrosine phosphorylation of p130(Cas), focal adhesion kinase, and paxillin. Role of phosphatidylinositol 3-kinase and formation of a pl30(Cas).Crk complex. J Biol Chem 1998; 273(40):26149–26156.

    PubMed  CAS  Google Scholar 

  78. Lee CH, Li W, Nishimura R et al. Nck associates with the SH2 domain-docking protein IRS-1 in insulin-stimulated cells. Proc Natl Acad Sci USA 1993; 90(24):11713–11717.

    PubMed  CAS  Google Scholar 

  79. Myers Jr MG, Backer JM, Sun XJ et al. IRS-1 activates phosphatidylinositol 3′-kinase by associating with src homology 2 domains of p85. Proc Natl Acad Sci USA 1992; 89(21):10350–10354.

    PubMed  CAS  Google Scholar 

  80. Alessi DR, Andjelkovic M, Caudwell B et al. Mechanism of activation of protein kinase B by insulin and IGF-1. Embo J 1996; 15(23):6541–6551.

    PubMed  CAS  Google Scholar 

  81. Parsons JT, Martin KH, Slack JK et al. Focal adhesion kinase: A regulator of focal adhesion dynamics and cell movement. Oncogene 2000; 19(49):5606–5613.

    PubMed  CAS  Google Scholar 

  82. Fujita Y, Krause G, Scheffner M et al. Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex. Nat Cell Biol 2002; 4(3):222–231.

    PubMed  CAS  Google Scholar 

  83. Kirchhausen T. Clathrin adaptors really adapt. Cell 2002; 109(4):413–416.

    PubMed  CAS  Google Scholar 

  84. Pearse BM, Smith CJ, Owen DJ. Clathrin coat construction in endocytosis. Curr Opin Struct Biol 2000; 10(2):220–228.

    PubMed  CAS  Google Scholar 

  85. Barbieri MA, Kohn AD, Roth RA et al. Protein kinase B/akt and rab5 mediate Ras activation of endocytosis. J Biol Chem 1998; 273(31):19367–19370.

    PubMed  CAS  Google Scholar 

  86. Grille SJ, Bellacosa A, Upson J et al. The protein kinase akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res 2003; 63(9):2172–2178.

    PubMed  CAS  Google Scholar 

  87. Sun XJ, Pons S, Asano T et al. The Fyn tyrosine kinase binds Irs-1 and forms a distinct signaling complex during insulin stimulation. J Biol Chem 1996; 271(18):10583–10587.

    PubMed  CAS  Google Scholar 

  88. Warren SL, Nelson WJ. Nonmitogenic morphoregulatory action of pp60v-src on multicellular epithelial structures. Mol Cell Biol 1987; 7(4):1326–1337.

    PubMed  CAS  Google Scholar 

  89. Tsukita S, Oishi K, Akiyama T et al. Specific proto-oncogenic tyrosine kinases of src family are enriched in cell-to-cell adherens junctions where the level of tyrosine phosphorylation is elevated. J Cell Biol 1991; 113(4):867–879.

    PubMed  CAS  Google Scholar 

  90. Ukropec JA, Hollinger MK, Salva SM et al. SHP2 association with VE-cadherin complexes in human endothelial cells is regulated by thrombin. J Biol Chem 2000; 275(8):5983–5986.

    PubMed  CAS  Google Scholar 

  91. Lee MM, Fink BD, Grunwald GB. Evidence that tyrosine phosphorylation regulates N-cadherin turnover during retinal development. Dev Genet 1997; 20(3):224–234.

    PubMed  CAS  Google Scholar 

  92. Lampugnani MG, Corada M, Andriopoulou P et al. Cell confluence regulates tyrosine phosphorylation of adherens junction components in endothelial cells. J Cell Sci 1997; 110(Pt 17):2065–2077.

    PubMed  CAS  Google Scholar 

  93. Daniel JM, Reynolds AB. Tyrosine phosphorylation and cadherin/catenin function. Bioessays 1997; 19(10):883–891.

    PubMed  CAS  Google Scholar 

  94. Esser S, Lampugnani MG, Corada M et al. Vascular endothelial growth factor induces VE-cadherin tyrosine phosphorylation in endothelial cells. J Cell Sci 1998; 111 (Pt 13):1853–1865.

    PubMed  CAS  Google Scholar 

  95. Nawroth R, Poell G, Ranft A et al. VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts. Embo J 2002; 21(18):4885–4895.

    PubMed  CAS  Google Scholar 

  96. Lickert H, Bauer A, Kemler R et al. Casein kinase II phosphorylation of E-cadherin increases E-cadherin/beta-catenin interaction and strengthens cell-cell adhesion. J Biol Chem 2000; 275(7):5090–5095.

    PubMed  CAS  Google Scholar 

  97. Roura S, Miravet S, Piedra J et al. Regulation of E-cadherin/Catenin association by tyrosine phosphorylation. J Biol Chem 1999; 274(51):36734–36740.

    PubMed  CAS  Google Scholar 

  98. Playford MP, Bicknell D, Bodmer WF et al. Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin. Proc Natl Acad Sci USA 2000; 97(22):12103–12108.

    PubMed  CAS  Google Scholar 

  99. Hu P, O’Keefe EJ, Rubenstein DS. Tyrosine phosphorylation of human keratinocyte beta-catenin and plakoglobin reversibly regulates their binding to E-cadherin and alpha-catenin. J Invest Dermatol 2001; 117(5):1059–1067.

    PubMed  CAS  Google Scholar 

  100. Rubinfeld B, Albert I, Porfiri E et al. Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science 1996; 272(5264):1023–1026.

    PubMed  CAS  Google Scholar 

  101. Hecht A, Kemler R. Curbing the nuclear activities of beta-catenin. Control over Wnt target gene expression. EMBO Rep 2000; 1(1):24–28.

    PubMed  CAS  Google Scholar 

  102. Huber AH, Nelson WJ, Weis WI. Three-dimensional structure of the armadillo repeat region of beta-catenin. Cell 1997; 90(5):871–882.

    PubMed  CAS  Google Scholar 

  103. Huber AH, Weis WI. The structure of the beta-catenin/E-cadherin complex and the molecular basis of diverse ligand recognition by beta-catenin. Cell 2001; 105(3):391–402.

    PubMed  CAS  Google Scholar 

  104. Graham TA, Weaver C, Mao F et al. Crystal structure of a beta-catenin/Tcf complex. Cell 2000; 103(6):885–896.

    PubMed  CAS  Google Scholar 

  105. Chen JW, Pan W, D’Souza MP et al. Lysosome-associated membrane proteins: Characterization of LAMP-1 of macrophage P388 and mouse embryo 3T3 cultured cells. Arch Biochem Biophys 1985; 239(2):574–586.

    PubMed  CAS  Google Scholar 

  106. Desbois-Mouthon C, Cadoret A, Blivet-Van Eggelpoel MJ et al. Insulin and IGF-1 stimulate the beta-catenin pathway through two signalling cascades involving GSK-3beta inhibition and Ras activation. Oncogene 2001; 20(2):252–259.

    PubMed  CAS  Google Scholar 

  107. Cross DA, Alessi DR, Cohen P et al. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 1995; 378(6559):785–789.

    PubMed  CAS  Google Scholar 

  108. Grevengoed EE, Loureiro JJ, Jesse TL et al. Abelson kinase regulates epithelial morphogenesis in Drosophila. J Cell Biol 2001; 155(7):1185–1198.

    PubMed  CAS  Google Scholar 

  109. Larue L, Antos C, Butz S et al. A role for cadherins in tissue formation. Development 1996; 122(10):3185–3194.

    PubMed  CAS  Google Scholar 

  110. Frame S, Cohen P, Biondi RM. A common phosphate binding site explains the unique substrate specificity of GSK3 and its inactivation by phosphorylation. Mol Cell 2001; 7(6):1321–1327.

    PubMed  CAS  Google Scholar 

  111. Dajani R, Fraser E, Roe SM et al. Crystal structure of glycogen synthase kinase 3 beta: Structural basis for phosphate-primed substrate specificity and autoinhibition. Cell 2001; 105(6):721–732.

    PubMed  CAS  Google Scholar 

  112. Fukumoto S, Hsieh CM, Maemura K et al. Akt participation in the Wnt signaling pathway through Dishevelled. J Biol Chem 2001; 276(20):17479–17483.

    PubMed  CAS  Google Scholar 

  113. Chen RH, Ding WV, McCormick F. Wnt signaling to beta-catenin involves two interactive components. Glycogen synthase kinase-3beta inhibition and activation of protein kinase C. J Biol Chem 2000; 275(23):17894–17899.

    PubMed  CAS  Google Scholar 

  114. Ding VW, Chen RH, McCormick F. Differential regulation of glycogen synthase kinase 3beta by insulin and Wnt signaling. J Biol Chem 2000; 275(42):32475–32481.

    PubMed  CAS  Google Scholar 

  115. Molenaar M, van de Wetering M, Oosterwegel M et al. XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. Cell 1996; 86(3):391–399.

    PubMed  CAS  Google Scholar 

  116. Behrens J, von Kries JP, Kuhl M et al. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature 1996; 382(6592):638–642.

    PubMed  CAS  Google Scholar 

  117. Huber O, Korn R, McLaughlin J et al. Nuclear localization of beta-catenin by interaction with transcription factor LEF-1. Mech Dev 1996; 59(1):3–10.

    PubMed  CAS  Google Scholar 

  118. Horb ME, Thomsen GH. A vegetally localized T-box transcription factor in Xenopus eggs specifies mesoderm and endoderm and is essential for embryonic mesoderm formation. Development 1997; 124(9):1689–1698.

    PubMed  CAS  Google Scholar 

  119. Papaioannou VE, Silver LM. The T-box gene family. Bioessays 1998; 20(1):9–19.

    PubMed  CAS  Google Scholar 

  120. Jacobs-Cohen RJ, Spiegelman M, Bennett D. Abnormalities of cells and extracellular matrix of T/T embryos. Differentiation 1983; 25(1):48–55.

    PubMed  CAS  Google Scholar 

  121. Wilson V, Manson L, Skarnes WC et al. The T gene is necessary for normal mesodermal morphogenetic cell movements during gastrulation. Development 1995; 121(3):877–886.

    PubMed  CAS  Google Scholar 

  122. Rashbass P, Wilson V, Rosen B et al. Alterations in gene expression during mesoderm formation and axial patterning in Brachyury (T) embryos. Int J Dev Biol 1994; 38(1):35–44.

    PubMed  CAS  Google Scholar 

  123. von Bredow DC, Nagle RB, Bowden GT et al. Degradation of fibronectin fibrils by matrilysin and characterization of the degradation products. Exp Cell Res 1995; 221(1):83–91.

    Google Scholar 

  124. Cuvelier A, Kuntz C, Sesboue R et al. Metalloproteinases in the extracellular matrix: Structure and activity. Rev Mal Respir 1997; 14(1):1–10.

    PubMed  CAS  Google Scholar 

  125. Delmas V et al. unpublished.

    Google Scholar 

  126. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2002; 2(6):442–454.

    PubMed  CAS  Google Scholar 

  127. Cano A, Perez-Moreno MA, Rodrigo I et al. The transcription factor snail controls epithelialmesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol 2000; 2(2):76–83.

    PubMed  CAS  Google Scholar 

  128. Batlle E, Sancho E, Franci C et al. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2000; 2(2):84–89.

    PubMed  CAS  Google Scholar 

  129. Comijn J, Berx G, Vermassen P et al. The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell 2001; 7(6):1267–1278.

    PubMed  CAS  Google Scholar 

  130. Perez-Moreno MA, Locascio A, Rodrigo I et al. A new role for E12/E47 in the repression of E-cadherin expression and epithelial-mesenchymal transitions. J Biol Chem 2001; 276(29):27424–27431.

    PubMed  CAS  Google Scholar 

  131. Rodrigo I, Cato AC, Cano A. Regulation of E-cadherin gene expression during tumor progression: The role of a new Ets-binding site and the E-pal element. Exp Cell Res 1999; 248(2):358–371.

    PubMed  CAS  Google Scholar 

  132. Morali OG, Jouneau A, McLaughlin KJ et al. IGF-II promotes mesoderm formation. Dev Biol 2000; 227(1):133–145.

    PubMed  CAS  Google Scholar 

  133. Sartor O, Cooper MR, Khleif SN et al. Suramin decreases circulating levels of insulin-like growth factor-I. Am J Med 1994; 96(4):390.

    PubMed  CAS  Google Scholar 

  134. Sell C, Dumenil G, Deveaud C et al. Effect of a null mutation of the insulin-like growth factor I receptor gene on growth and transformation of mouse embryo fibroblasts. Mol Cell Biol 1994; 14(6):3604–3612.

    PubMed  CAS  Google Scholar 

  135. Xie SP, Pirianov G, Colston KW. Vitamin D analogues suppress IGF-I signalling and promote apoptosis in breast cancer cells. Eur J Cancer 1999; 35(12):1717–1723.

    PubMed  CAS  Google Scholar 

  136. Hogan B, Beddington R, Costantini F et al. Manipulating the mouse embryo: A laboratory manual. Cold Spring Harbor Laboratory Press, 1994.

    Google Scholar 

  137. Lee JE, Pintar J, Efstratiadis A. Pattern of the insulin-like growth factor II gene expression during early mouse embryogenesis. Development 1990; 110(1):151–159.

    PubMed  CAS  Google Scholar 

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Julien-Grille, S. et al. (2005). The Role of Insulin-Like Growth Factors in the Epithelial to Mesenchymal Transition. In: Rise and Fall of Epithelial Phenotype. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-28671-3_14

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