Advertisement

Journal of Molecular Histology

, Volume 35, Issue 3, pp 247–253 | Cite as

IGF-I Receptor, Cell–Cell Adhesion, Tumour Development and Progression

  • Loredana Mauro
  • Eva Surmacz
Article

Abstract

The insulin-like growth factor I receptor (IGF-IR) has been implicated in the development and progression of many common cancers and other neoplastic diseases. The tumorigenic potential of IGF-IR relies on its antiapoptotic and transforming activities. The molecular mechanisms by which IGF-IR controls the proliferation and survival of tumour cells have been extensively studied and many pathways have been delineated. However, the role of IGF-IR in the regulation of non-mitogenic cell functions is less well understood. Here we focus on IGF-IR-dependent cell–cell adhesion. Limited studies suggested that IGF-IR can regulate cell aggregation and intercellular adhesion mediated by cadherins and cadherin-associated proteins. We review the mechanisms of this process and discuss the impact of IGF-IR-dependent cell–cell adhesion on the phenotype of tumour cells.

Keywords

Tumour Cell Growth Factor Molecular Mechanism Cell Adhesion Cell Function 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aberle H, Schwartz H, Hemler R (1996) Cadherin-catenin complex: Protein interactions and their implications for cadherin function. J Cell Biochem 61: 514–523.Google Scholar
  2. Adams TE, Epa VC, Garrett TP, Ward CW(2000) Structure and function of the type 1 insulin-like growth factor receptor. Cell Mol Life Sci 57: 1050–1093.Google Scholar
  3. Anastasiadis PZ, Reynolds AB (2001) Regulation of Rho GTPases by p120-catenin. Curr Opin Cell Biol 13: 604–610.Google Scholar
  4. Anastasiadis PZ, Moon SY, Thoreson MA, Mariner DJ, Crawford HC, Zheng Y, Reynolds AB (2000) Inhibition of RhoA by p120 catenin. Nature Cell Biol 2: 637–644.Google Scholar
  5. Andre' F, Rigot V, Thimonier J, Montixi C, Parat F, Pommier G, Marvaldi J, Luis J (1999) Integrins and E-cadherin cooperate with IGF-I to induce migration of epithelial colonic cells. Int J Cancer 83: 497–505.Google Scholar
  6. Baron V, Calleja V, Ferrari P, Alengrin F, Van Obberghen E (1998) p125 Fak focal adhesion kinase is a substrate for the insulin and insulin-like growth factor-I tyrosine kinase receptors. J Biol Chem 273: 7162–7168.Google Scholar
  7. Baserga R (1994) Oncogenes and the strategy of growth factors. Cell 79: 927–930.Google Scholar
  8. Baserga R (1995) The insulin-like growth factor I receptor: A key to tumour growth? Cancer Res 55: 249–252.Google Scholar
  9. Baserga R (1998) The IGF-IR in normal and abnormal growth. In: Dickson R, Salomon DS, eds. Hormone and Growth Factors in Development and Neoplasia. Wiley-Liss, NewYork, NY. pp. 269–287.Google Scholar
  10. Becker KF, Atkinson MJ, Reich I, Nekarda H, Siewert JR, Hofter H (1994) E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. Cancer Res 54: 3845–3852.Google Scholar
  11. Beitner-Johnson D, LeRoith D (1995) Insulin-like growth factor-I stimulates tyrosine phosphorylation of endogenous c-Crk. J Biol Chem 270: 5187–5190.Google Scholar
  12. Ben-Ze'ev A (1997) Cytoskeletal and adhesion proteins as tumour suppressors. Curr Opin Cell Biol 9: 99–108.Google Scholar
  13. Bienz M, Clevers H (2000) Linking colorectal cancer Wnt signaling. Cell 103: 311–320.Google Scholar
  14. Birchmeier W, Behrens J (1994) Cadherin expression in carcinomas: Role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta 1198: 11–26.Google Scholar
  15. Bracke ME, Vyncke BM, Bruyneel EA, Vermeulen SJ, De Bruyne GK, Van Larebeke NA, Vleminckx K, Van Roy FM, Mareel MM (1993) Insulin-like growth factor I activates the invasion suppressor function of E-cadherin in MCF-7 human mammary carcinoma cells in vitro. Br J Cancer 68: 282–289.Google Scholar
  16. Brazil DP, Park J, Hemmings BA (2002) PKB binding proteins. Getting in on the Akt. Cell 111: 293–303.Google Scholar
  17. Bullions L, Notterman D, Chung L, Levine A (1997) Expression of wild-type á-catenin protein in cells with a mutant á-catenin gene restores both growth regulation and tumour suppressor activities. Mol Cell Biol 17: 4501–4508.Google Scholar
  18. Burroughs KD, Howe SR, Okubo Y, Fuchs-Young R, LeRoith D, Walker CL (2002) Dysregulation of IGF-I signaling in uterine leiomyoma. J Endocrinol 172: 83–93.Google Scholar
  19. Casamassima A, Rozengurt E (1998) 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 p130 (Cas). Crk complex. J Biol Chem 273: 26149–26156.Google Scholar
  20. Chattopadhyay A, Carpenter G (2002) PLC-ã 1 is required for IGF-I protection from cell death induced by loss of extracellular matrix adhesion. J Cell Sci 115: 2233–2239.Google Scholar
  21. Clemmons DR, Maile LA (2003) Minireview: Integral membrane proteins that function coordinately with the insulin-like growth factor I receptor to regulate intracellular signaling. Endocrinol 144: 1664–1670.Google Scholar
  22. Daniel JM, Reynolds AB (1995) The tyrosine kinase substrate p120 cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or á-catenin. Mol Cell Biol 15: 4819–4824.Google Scholar
  23. Deman JJ, Van Larebeke NA, Bruyneel EA, Bracke ME, Vermeulen SJ, Vennekens KM, Mareel MM (1995) Removal of sialic acid from the surface of human MCF-7 mammary cancer cells abolished E-cadherin-dependent cell-cell adhesion in an aggregation assay. In Vitro Cell Dev Biol Anim 31: 633–639.Google Scholar
  24. Djavan B, Waldert M, Seitz C, Marberger M (2001) Insulin-like growth factors and prostate cancer. World J Urol 19: 225–233.Google Scholar
  25. Doerr M, Jones J (1996) The roles of integrins and extracellular matrix proteins in the IGF-IR-stimulated chemotaxis of human breast cancer cells. J Biol Chem 271: 2443–2447.Google Scholar
  26. Druckmann R, Rohr UD (2002) IGF-1 in gynecology and obstetrics: Update. Maturitas 41: S65-S83.Google Scholar
  27. Dunn SE, Torres JV, Nihei N, Barrett JC (2000) The insulin-like growth factor-1 elevates urokinase-type plasminogen activator-1 in human breast cancer cells: A new avenue for breast cancer therapy. Mol Carcinog 27: 10–17.Google Scholar
  28. Fukata M, Nakagawa M, Kuroda S, Kaibichi K (1999) Cell adhesion and Rho small GTPases. J Cell Sci 112: 4491–4500.Google Scholar
  29. Garrouste F, Remacle-Bonnet M, Faurlat C, Marvaldi J, Luis J, Pommier G (2002) Prevention of cytokine-induced apoptosis by insulin-like growth factor I is independent of cell adhesion molecules in HT29-D4 colon carcinoma cells-evidence for a NF-ê B-dependent survival mechanism. Cell Death Differ 9: 768–779.Google Scholar
  30. Giovannucci E (2001) Insulin, insulin-like growth factors and colon cancer: A review of the evidence. J Nutr 131: 3109S-3120S.Google Scholar
  31. Gottardi C, Wong E, Gumbiner B (2001) E-cadherin suppresses cellular transformation by inhibiting â-catenin signaling in an adhesion independent manner J Cell Biol 153: 1049–1060.Google Scholar
  32. Grosheva I, Shtutman M, Elbaum M, Bershadsky AD(2001) p120 catenin affects cell motility via modulation of activity of Rho-family GTPases: A link between cell-cell contact formation and regulation of cell locomotion. J Cell Sci 114: 695–707.Google Scholar
  33. Guerra FK, Eijan AM, Puricelli L, Alonso DF, de Kier Joffe E, Kornblihtt AR, Charreau EH, Elizalde PV (1996) Varying patterns of expression of insulin-like growth factors I and II and their receptors in murine mammary adenocarcinomas of different metastasizing ability. Int J Cancer 65: 812–820.Google Scholar
  34. Gumbiner BM (1996) Cell adhesion: The molecular basis of tissue architecture and morphogenesis. Cell 84: 345–357.Google Scholar
  35. Guvakova MA, Surmacz E (1997) 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 231: 149–162.Google Scholar
  36. Guvakova MA, Surmacz E (1999) The activated insulin-like growth factor I receptor induces depolarization in breast epithelial cells characterized by actin filament disassembly and tyrosine dephos-phorylation of FAK, Cas, and paxillin. Exp Cell Res 251: 244–255.Google Scholar
  37. Hall A (1998) Rho GTPases and the actin cytoskeleton. Science 279: 509–514.Google Scholar
  38. He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW (1998) Identification of cMYC as a target of the APC pathway. Science 281: 1509–1512.Google Scholar
  39. Hermanto U, Zong CS, Li W, Wang L-H (2002) Rack1, and insulin-like growth factor I (IGF-I) receptor-interacting protein, modulates IGF-I-dependent integrin signaling and promotes cell spreading and contact with extracellular matrix. Mol Cell Biol 22: 2345–2365.Google Scholar
  40. Hill MM, Hemmings BA (2002) Inhibition of protein kinase B/Akt: Implications for cancer therapy. Pharmacol Ther 93: 243–251.Google Scholar
  41. Hirano S, Kimoro N, Shimoyama Y, Hirohashi S, Takeichi M (1992) Identification of a neural á-catenin as a key regulator of cadherin function and multicellular organization. Cell 70: 293–301.Google Scholar
  42. Huber O, Bierkamp C, Kemler R (1996) Cadherins and catenins in development. Curr Opin Cell Biol 8: 685–691.Google Scholar
  43. Ireton RC, Davis MA, van Hengel J, Mariner DJ, Barnes K, Thoreson MA, Anastasiadis PZ, Matrisian L, Bundy LM, Sealy L, Gilbert B, van Roy F, Reynolds AB (2002) A novel role for p120 catenin in E-cadherin function. J Cell Biol 159: 465–476.Google Scholar
  44. Kaleko M, Rutter WJ, Miller AD (1990) Overexpression of the human insulin-like growth factor I receptor promotes ligand-dependent neo-plastic transformation. Mol Cell Biol 10: 464–473.Google Scholar
  45. Korc M (1998) Role of growth factors in pancreatic cancer. Surg Oncol Clin N Am 7: 25–41.Google Scholar
  46. Koval AP, Karas M, Zick Y, LeRoith D (1998) Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction. J Biol Chem 273: 14780–14787.Google Scholar
  47. Long L, Rubin R, Brodt P (1998) Enhanced invasion and liver coloniza-tion by lung carcinoma cells overexpressing the type 1 insulin-like growth factor receptor. Exp Cell Res 238: 116–121.Google Scholar
  48. Mauro L, Bartucci M, Morelli C, Ando' S, Surmacz E (2001) IGF-I receptor-induced cell-cell adhesion of MCF-7 breast cancer cells requires the expression of junction protein ZO-1. J Biol Chem 276: 39892–39897.Google Scholar
  49. Mauro L, Salerno M, Morelli C, Boterberg T, Bracke ME, Surmacz E (2003) Role of the IGF-I receptor in the regulation of cell-cell adhe-sion: Implication in cancer development and progression. J Cell Physiol 194: 108–116.Google Scholar
  50. Mauro L, Sisci D, Bartucci M, Salerno M, Kim J, Tam T, Guvakova MA, Ando' S, Surmacz E (1999) SHC-alpha5beta1 integrin interactions regulate breast cancer cell adhesion and motility. Exp Cell Res 252: 439–448.Google Scholar
  51. Mira E, Manes S, Lacalle RA, Marquez G, Martinez-A C (1999) Insulin-like growth factor I-triggered cell migration and invasion are mediated by matrix metalloproteinase-9. Endocrinology 140: 1657–1664.Google Scholar
  52. Morford LA, Boghaert E, Brooks W, Roszman TL (1997) Insulin-like growth factors (IGF) enhance three-dimensional (3D) growth of human glioblastomas. Cancer Lett 115: 81–90.Google Scholar
  53. Navarro P, Lozano E, Cano A(1993) Expression of E-or P-cadherin is not sufficient to modify the morphology and the tumourigenic behavior of murine spindle carcinoma cells: Possible involvement of plakoglobin. J Cell Sci 105: 923–934.Google Scholar
  54. Nicholson KM, Anderson N (2002) The protein kinase B/Akt signaling in human malignancy. Cell Signal 14: 381–395.Google Scholar
  55. Noren NK, Liu BP, Birridge K, Kreft B (2000) p120 catenin regulates the actin cytoskeleton via Rho family GTPases. J Cell Biol 150: 567–580.Google Scholar
  56. Nose A, Nagafuchi A, Takeichi M (1988) Expressed recombinant cadherins mediate cell sorting in model systems. Cell 54: 993–1001.Google Scholar
  57. O'Connor R, Fennelly C, Krause D (2000) Regulation of survival signals from the insulin-like growth factor-I receptor. Biochem Soc Trans 28: 47–51.Google Scholar
  58. Ozawa M, Kemler R (1998) The membrane-proximal region of the E-cadherin cytoplasmic domain prevents dimerization and negatively regulates adhesion activity. J Cell Biol 142: 1605–1613.Google Scholar
  59. Peifer M, Berg S, Reynolds AB (1994) A repeating amino acid motif shared by proteins with diverse cellular roles. Cell 6: 789–791.Google Scholar
  60. Pennisi PA, Barr V, Nunez NP, Stannard B, LeRoith D (2002) Reduced expression of insulin-like growth factor I receptors in MCF-7 breast cancer cells leads to a more metastatic phenotype. Cancer Res 62: 6529–6537.Google Scholar
  61. Peruzzi F, Prisco M, Dews M, Salomoni P, Grassilli E, Romano G, Calabretta B, Baserga R (1999) Multiple signaling pathways of the insulin-like growth factor 1 receptor in protection from apoptosis. Mol Cell Biol 19: 7203–7215.Google Scholar
  62. Pierceall WE, Woodward AS, Morrow JS, Rimm D, Fearon ER (1995) Frequent alterations in E-cadherin and á-and â-catenin expression in human breast cancer cell lines. Oncogene 11: 1319–1326.Google Scholar
  63. Pietrzkowski Z, Lammers R, Carpenter G, Soderquist AM, Limardo M, Phillips PD, Ullrich A, Baserga R (1992) Constitutive expression of insulin-like growth factor 1 and insulin-like growth factor 1 receptor abrogates all requirements for exogenous growth factors. Cell Growth Differ 3: 199–205.Google Scholar
  64. Playford MP, Bicknell D, Bodmer WF, Macaulay VM(2000) Insulin-like growth factor 1 regulates the location, stability, and transcriptional of beta-catenin activity. Proc Natl Acad Sci USA 97: 12103–12108.Google Scholar
  65. Polakis P, Hart M, Rubinfeld B (1999) Defects in the regulation of beta-catenin in colorectal cancer. Adv Exp Med Biol 470: 23–32.Google Scholar
  66. Pollak M (2000) Insulin-like growth factor physiology and cancer risk. Eur J Cancer 36: 1224–1228.Google Scholar
  67. Provost E, Rimm DL (1999) Controversies at the cytoplasmic face of the cadherin-based adhesion complex. Curr Opin Cell Biol 11: 567–572.Google Scholar
  68. Reiss K, Wang JY, Romano G, Tu X, Peruzzi F, Baserga R (2001) Mechanisms of regulation of cell adhesion and motility by insulin receptor substrate-1 in prostate cancer cells. Oncogene 20: 490–500.Google Scholar
  69. Reynolds AB, Roesel DJ, Kanner SB, Parson JT (1989) Transformation specific tyrosine phosphorylation of a novel cellular protein in chicken cells expression oncogenic variants of the avian cellular src gene. Mol Cell Biol 9: 629–638.Google Scholar
  70. Reynolds AB, Herbert L, Cleveland JL, Berg ST, Gaut JR (1992) p120, a novel substrate of protein tyrosine kinase receptors and of p60 v-src, is related to cadherin-binding factor â-catenin, plakoglobin and armadillo. Oncogene 7: 2439–2445.Google Scholar
  71. Reynolds AB, Daniel J, McCeca PD, Wheelock MJ, Wu J, Zhang Z (1994) Identification of a new catenin: the tyrosine kinase substrate p120 cas associates with E-cadherin complexes. Mol Cell Biol 14: 8333–8342.Google Scholar
  72. Sachdev D, Yee D (2001) The IGF system and breast cancer. Endocr Relat Cancer 8: 197–209.Google Scholar
  73. Scharf JG, Dombrowski F, Ramadori G (2001) The IGF axis and hepatocarcinogenesis. Mol Pathol 54: 138–144.Google Scholar
  74. Shapiro L, Fannon AM, Kwong PD, Thompson A, Lehmann MS, Grubel G, Legrand J-F, Als-Nielsen J, Colman DR, Hendrickson WA (1995) Structural basis of cell-cell adhesion by cadherins. Nature 374: 327–337.Google Scholar
  75. Shaw LM(2001) Identification of insulin receptor substrate 1 (IRS-1) and IRS-2 as signaling intermediates in the alpha6beta4 integrin-dependent activation of phosphoinositide 3-OH kinase and promotion of invasion. Mol Cell Biol 21: 5082–5093.Google Scholar
  76. Shibamoto S, Hayakawa M, Takeuchi K, Hori T, Miyazawa K, Kitamura N, Johnson KR, Wheelock MJ, Matsuyoshi N, Takeichi M (1995) Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complex. J Cell Biol 128: 949–957.Google Scholar
  77. 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 â-catenin/LEF-1 pathway. Proc Natl Acad Sci USA 96: 5522–5527.Google Scholar
  78. Sommers CL, Gelmann EP, Kemler R, Cowin P, Byers SW (1994) Alterations in â-catenin phosphorylation and plakoglobin expression in human breast cancer cells. Cancer Res 54: 3544–3552.Google Scholar
  79. Staddon JM, Smales C, Schulze C, Esch FS, Rubin LL (1995) p120 a p120-related protein (p100), and the cadherin/catenin complex. J Cell Biol 130: 369–381.Google Scholar
  80. Steinberg MS (1996) Adhesion in development: A historical overview. Dev Biol 180: 377–388.Google Scholar
  81. Stockinger A, Eger A, Wolf J, Beug H, Foisner R (2001) E-cadherin regulates cell growth by modulating proliferation-dependent â-catenin transcriptional activity. J Cell Biol 154: 1185–1196.Google Scholar
  82. Surmacz E (2000) Function of the IGF-IR in breast cancer. J Mammary Gland Biol Neopl 5: 95–105.Google Scholar
  83. Surmacz E (2003) Growth factor receptors as therapeutic targets: Strategies to inhibit the insulin-like growth factor I receptor. Oncogene 22: 6589–6597.Google Scholar
  84. Surmacz E, Guvakova MA, Nolan MK, Nicosia RF, Sciacca L (1998) Type I insulin-like growth factor receptor function in breast cancer. Breast Cancer Res Treat 47: 255–267.Google Scholar
  85. Takai Y, Sasaki T, Matozaki T (2001) Small GTP-binding proteins. Physiol Rev 81: 153–208.Google Scholar
  86. Takeichi M (1995) Morphogenetic roles of classic cadherins. Curr Opin Cell Biol 7: 619–627.Google Scholar
  87. Tetsu O, McCormick F (1999) â-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398: 422–426.Google Scholar
  88. Thoreson MA, Anastasiadis PZ, Daniel JM, Ireton RC, Wheelock KR, Johnson DK, Hummingbird DK, Reynolds AB (2000) Selective uncoupling of p120(ctn) from E-cadherin disrupts strong adhesion. J Cell Biol 148: 189–202.Google Scholar
  89. Ullrich A, Gray A, Tam AW, Yang-Feng T, Tsubokawa M, Collins C, Henzel W, Le Bon T, Kathuria S, Chen E, Jacobs S, Fraucke U, Ramachandran J, Fujita-Yamaguchi Y. (1986) Insulin-like growth fac-tor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J 5: 2503–2512.Google Scholar
  90. Valentinis B, Morrione A, Peruzzi F, Prisco M, Reiss K, Baserga R(1999) Anti-apoptotic signaling of the IGF-I receptor in fibroblasts following loss of matrix adhesion. Oncogene 18: 1827–1836.Google Scholar
  91. Vermeulen SJ, Bruyneel EA, Bracke ME, De Bruyne GK, Vennekens KM, Vlemincks KL, Berx GL, Van Roy FM, Mareel MM (1995) Transition from the noninvasive to the invasive phenotype and loss of á-catenin in human colon cancer. Cancer Res 55: 4722–4728.Google Scholar
  92. Vleminckx K, Kemler R (1999) Cadherins and tissue formation: Integrating adhesion and signaling. Bioessays 21: 211–220.Google Scholar
  93. Vleminckx KL, Vakaet J, Mareel M, Fiers W, Van Roy F (1991) Genetic manipulation of E-cadherin expression by epithelial tumour cells reveals an invasion suppressor role. Cell 66: 107–119.Google Scholar
  94. Vuori K, Ruoslahti E (1994) Association of insulin receptor substrate 1 with integrins. Science 266: 1576–1578.Google Scholar
  95. Wary KK, Mainiero F, Isakoff, SJ, Marcantonio EE, Giancotti FG (1996) The adaptor protein Shc couples a class of integrins to the control of cell cycle progression. Cell 87: 733–743.Google Scholar
  96. Watanabe H, Miura M, Sasaki T (1999) Differential effects of the insulin-like growth factor I receptor on radiosensitivity and spontaneous necrosis formation of human glioblastoma cells grown in multicellular spheroids. Exp Cell Res 250: 99–111.Google Scholar
  97. White MF (1998) The IRS-signalling system: A network of dock-ing proteins that mediate insulin action. Mol Cell Biochem 182: 3–11.Google Scholar
  98. White MF (2002) IRS proteins and the common path to diabetes. Am J Physiol Endocrinol Metab 283: E413-E422.Google Scholar
  99. Zong CS, Chan J, Levy DE, Horvath C, Sadowski HB, Wang LH (2000) Mechanism of STAT3 activation by insulin-like growth factor I receptor. J Biol Chem 275: 15099–15105.Google Scholar
  100. Zong CS, Zeng L, Jiang Y, Sadowski HB, Wang LH (1998) Stat3 plays an important role in oncogenic Ros-and insulin-like growth factor I receptor-induced anchorage-independent growth. J Biol Chem 273: 28065–28072.Google Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Loredana Mauro
    • 1
  • Eva Surmacz
    • 2
  1. 1.Department of Cellular Biology and Faculty of PharmacyUniversity of CalabriaRendeItaly
  2. 2.Kimmel Cancer InstituteThomas Jefferson UniversityPhiladelphiaUSA;

Personalised recommendations