About this Journal Submit a Manuscript Table of Contents
Journal of Oncology
Volume 2011 (2011), Article ID 352616, 19 pages
http://dx.doi.org/10.1155/2011/352616
Review Article

Loss of Function of E-Cadherin in Embryonic Stem Cells and the Relevance to Models of Tumorigenesis

Core Technology Facility, Faculty of Medical and Human Sciences, The University of Manchester, 46 Grafton Street, Manchester M13 9NT, UK

Received 1 August 2010; Revised 15 October 2010; Accepted 26 October 2010

Academic Editor: Eric Deutsch

Copyright © 2011 Lisa Mohamet et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. U. Cavallaro and G. Christofori, “Cell adhesion and signalling by cadherins and Ig-CAMs in cancer,” Nature Reviews Cancer, vol. 4, no. 2, pp. 118–132, 2004. View at Scopus
  2. O. Pertz, D. Bozic, A. W. Koch, C. Fauser, A. Brancaccio, and J. Engel, “A new crystal structure, Ca2+ dependence and mutational analysis reveal molecular details of E-cadherin homoassociation,” The EMBO Journal, vol. 18, no. 7, pp. 1738–1747, 1999. View at Scopus
  3. F. Van Roy and G. Berx, “The cell-cell adhesion molecule E-cadherin,” Cellular and Molecular Life Sciences, vol. 65, no. 23, pp. 3756–3788, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. M. Perez-Moreno and E. Fuchs, “Catenins: keeping cells from getting their signals crossed,” Developmental Cell, vol. 11, no. 5, pp. 601–612, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. P. D. McCrea and J.-I. Park, “Developmental functions of the P120-catenin sub-family,” Biochimica et Biophysica Acta - Molecular Cell Research, vol. 1773, no. 1, pp. 17–33, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  6. K. Ling, S. F. Bairstow, C. Carbonara, D. A. Turbin, D. G. Huntsman, and R. A. Anderson, “Type Iγ phosphatidylinositol phosphate kinase modulates adherens junction and E-cadherin trafficking via a direct interaction with μ 1B adaptin,” Journal of Cell Biology, vol. 176, no. 3, pp. 343–353, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  7. U. Cavallaro, B. Schaffhauser, and G. Christofori, “Cadherins and the tumour progression: is it all in a switch?” Cancer Letters, vol. 176, no. 2, pp. 123–128, 2002. View at Publisher · View at Google Scholar
  8. L. Di Croce and P. G. Pelicci, “Tumour-associated hypermethylation: silencing E-cadherin expression enhances invasion and metastasis,” European Journal of Cancer, vol. 39, no. 4, pp. 413–414, 2003. View at Publisher · View at Google Scholar
  9. A. Margulis, W. Zhang, A. Alt-Holland, H. C. Crawford, N. E. Fusenig, and J. A. Garlick, “E-cadherin suppression accelerates squamous cell carcinoma progression in three-dimensional, human tissue constructs,” Cancer Research, vol. 65, no. 5, pp. 1783–1791, 2005. View at Publisher · View at Google Scholar · View at PubMed
  10. U. Cavallaro and G. Christofori, “Multitasking in tumor progression: signaling functions of cell adhesion molecules,” Annals of the New York Academy of Sciences, vol. 1014, pp. 58–66, 2004. View at Publisher · View at Google Scholar
  11. M. A. Nieto, “The snail superfamily of zinc-finger transcription factors,” Nature Reviews Molecular Cell Biology, vol. 3, no. 3, pp. 155–166, 2002. View at Publisher · View at Google Scholar · View at PubMed
  12. V. Bolós, H. Peinado, M. A. Pérez-Moreno, M. F. Fraga, M. Esteller, and A. Cano, “The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors,” Journal of Cell Science, vol. 116, no. 3, pp. 499–511, 2003. View at Publisher · View at Google Scholar
  13. M. Polette, B. Nawrocki-Raby, C. Gilles, C. Clavel, and P. Birembaut, “Tumour invasion and matrix metalloproteinases,” Critical Reviews in Oncology/Hematology, vol. 49, no. 3, pp. 179–186, 2004. View at Publisher · View at Google Scholar · View at PubMed
  14. B. Nawrocki-Raby, C. Gilles, M. Polette et al., “Upregulation of MMPS by soluble E-cadherin in human lung tumor cells,” International Journal of Cancer, vol. 105, no. 6, pp. 790–795, 2003. View at Publisher · View at Google Scholar · View at PubMed
  15. S. Crouch, C. S. Spidel, and J. S. Lindsey, “HGF and ligation of αvβ5 integrin induce a novel, cancer cell-specific gene expression required for cell scattering,” Experimental Cell Research, vol. 292, no. 2, pp. 274–287, 2004. View at Publisher · View at Google Scholar
  16. M. Murai, X. Shen, L. Huang et al., “Overexpression of c-met in oral SCC promotes hepatocyte growth factor-induced disruption of cadherin junctions and invasion,” International journal of oncology, vol. 25, no. 4, pp. 831–840, 2004.
  17. H. Khoury, M. A. Naujokas, D. Zuo et al., “HGF converts ErbB2/Neu epithelial morphogenesis to cell invasion,” Molecular Biology of the Cell, vol. 16, no. 2, pp. 550–561, 2005. View at Publisher · View at Google Scholar · View at PubMed
  18. F. H. Brembeck, M. Rosário, and W. Birchmeier, “Balancing cell adhesion and Wnt signaling, the key role of β-catenin,” Current Opinion in Genetics and Development, vol. 16, no. 1, pp. 51–59, 2006. View at Publisher · View at Google Scholar · View at PubMed
  19. M. Watabe, A. Nagafuchi, S. Tsukita, and M. Takeichi, “Induction of polarized cell-cell association and retardation of growth by activation of the E-cadherin-catenin adhesion system in a dispersed carcinoma line,” Journal of Cell Biology, vol. 127, no. 1, pp. 247–256, 1994. View at Publisher · View at Google Scholar
  20. P. Doherty and F. S. Walsh, “CAM-FGF receptor interactions: a model for axonal growth,” Molecular and Cellular Neurosciences, vol. 8, no. 2-3, pp. 99–111, 1996. View at Publisher · View at Google Scholar
  21. D. Stenzel, E. Nye, M. Nisancioglu, R. H. Adams, Y. Yamaguchi, and H. Gerhardt, “Peripheral mural cell recruitment requires cell-autonomous heparan sulfate,” Blood, vol. 114, no. 4, pp. 915–924, 2009. View at Publisher · View at Google Scholar · View at PubMed
  22. J. Heasman, A. Crawford, K. Goldstone et al., “Overexpression of cadherins and underexpression of β-catenin inhibit dorsal mesoderm induction in early xenopus embryos,” Cell, vol. 79, no. 5, pp. 791–803, 1994. View at Publisher · View at Google Scholar
  23. M. Bienz and H. Clevers, “Linking colorectal cancer to Wnt signaling,” Cell, vol. 103, no. 2, pp. 311–320, 2000.
  24. C. J. Gottardi and B. M. Gumbiner, “Distinct molecular forms of β-catenin are targeted to adhesive or transcriptional complexes,” Journal of Cell Biology, vol. 167, no. 2, pp. 339–349, 2004. View at Publisher · View at Google Scholar · View at PubMed
  25. M. Goodwin, E. M. Kovacs, M. A. Thoreson, A. B. Reynolds, and A. S. Yap, “Minimal mutation of the cytoplasmic tail inhibits the ability of E-cadherin to activate Rac but not phosphatidylinositol 3-kinase. Direct evidence of a role for cadherin-activated Rac signaling in adhesion and contact formation,” Journal of Biological Chemistry, vol. 278, no. 23, pp. 20533–20539, 2003. View at Publisher · View at Google Scholar · View at PubMed
  26. J. P. Thiery, “Cell adhesion in development: a complex signaling network,” Current Opinion in Genetics and Development, vol. 13, no. 4, pp. 365–371, 2003. View at Publisher · View at Google Scholar
  27. N. K. Noren, C. M. Niessen, B. M. Gumbiner, and K. Burridge, “Cadherin engagement regulates Rho family GTPases,” Journal of Biological Chemistry, vol. 276, no. 36, pp. 33305–33308, 2001. View at Publisher · View at Google Scholar · View at PubMed
  28. G. S. Martin, “Cell signaling and cancer,” Cancer Cell, vol. 4, no. 3, pp. 167–174, 2003. View at Publisher · View at Google Scholar
  29. A. G. Smith, “Embryo-derived stem cells: of mice and men,” Annual Review of Cell and Developmental Biology, vol. 17, pp. 435–462, 2001.
  30. J. Ringe, C. Kaps, G.-R. Burmester, and M. Sittinger, “Stem cells for regenerative medicine: advances in the engineering of tissues and organs,” Naturwissenschaften, vol. 89, no. 8, pp. 338–351, 2002. View at Publisher · View at Google Scholar · View at PubMed
  31. L. Larue, C. Antos, S. Butz et al., “A role for cadherins in tissue formation,” Development, vol. 122, no. 10, pp. 3185–3194, 1996.
  32. J. M. Lee, S. Dedhar, R. Kalluri, and E. W. Thompson, “The epithelial-mesenchymal transition: new insights in signaling, development, and disease,” Journal of Cell Biology, vol. 172, no. 7, pp. 973–981, 2006. View at Publisher · View at Google Scholar · View at PubMed
  33. A. M. Eastham, H. Spencer, F. Soncin et al., “Epithelial-mesenchymal transition events during human embryonic stem cell differentiation,” Cancer Research, vol. 67, no. 23, pp. 11254–11262, 2007. View at Publisher · View at Google Scholar · View at PubMed
  34. H. L. Spencer, A. M. Eastham, C. L. R. Merry et al., “E-cadherin inhibits cell surface localization of the pro-migratory 5T4 oncofetal antigen in mouse embryonic stem cells,” Molecular Biology of the Cell, vol. 18, no. 8, pp. 2838–2851, 2007. View at Publisher · View at Google Scholar · View at PubMed
  35. U. Ullmann, P. In't Veld, C. Gilles et al., “Epithelial-mesenchymal transition process in human embryonic stem cells cultured in feeder-free conditions,” Molecular Human Reproduction, vol. 13, no. 1, pp. 21–32, 2007. View at Publisher · View at Google Scholar · View at PubMed
  36. R. Behr, C. Heneweer, C. Viebahn, H.-W. Denker, and M. Thie, “Epithelial-mesenchymal transition in colonies of rhesus monkey embryonic stem cells: a model for processes involved in gastrulation,” Stem Cells, vol. 23, no. 6, pp. 805–816, 2005. View at Publisher · View at Google Scholar · View at PubMed
  37. A. Wicki, F. Lehembre, N. Wick, B. Hantusch, D. Kerjaschki, and G. Christofori, “Tumor invasion in the absence of epithelial-mesenchymal transition: podoplanin-mediated remodeling of the actin cytoskeleton,” Cancer Cell, vol. 9, no. 4, pp. 261–272, 2006. View at Publisher · View at Google Scholar · View at PubMed
  38. J. J. Christiansen and A. K. Rajasekaran, “Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis,” Cancer Research, vol. 66, no. 17, pp. 8319–8326, 2006. View at Publisher · View at Google Scholar · View at PubMed
  39. S. Orsulic and R. Kemler, “Expression of Eph receptors and ephrins is differentially regulated by E-cadherin,” Journal of Cell Science, vol. 113, no. 10, pp. 1793–1802, 2000.
  40. H. Andersen, J. Mejlvang, S. Mahmood et al., “Immediate and delayed effects of E-cadherin inhibition on gene regulation and cell motility in human epidermoid carcinoma cells,” Molecular and Cellular Biology, vol. 25, no. 20, pp. 9138–9150, 2005. View at Publisher · View at Google Scholar · View at PubMed
  41. P. J. Southall, G. M. Boxer, K. D. Bagshawe, N. Hole, M. Bromley, and P. L. Stern, “Immunohistological distribution of 5T4 antigen in normal and malignant tissues,” British Journal of Cancer, vol. 61, no. 1, pp. 88–95, 1990.
  42. T. Starzynska, A. Wiechowska-Kozlowska, K. Marlicz et al., “The clinical significance of 5T4 antigen in gastric carcinoma,” Gut, vol. 41, p. A194, 1997.
  43. T. Starzynska, P. J. Marsh, P. F. Schofield, S. A. Roberts, K. A. Myers, and P. L. Stern, “Prognostic significance of 5T4 oncofetal antigen expression in colorectal carcinoma,” British Journal of Cancer, vol. 69, no. 5, pp. 899–902, 1994.
  44. T. Starzynska, V. Rahi, and P. L. Stern, “The expression of 5T4 antigen in colorectal and gastric carcinoma,” British Journal of Cancer, vol. 66, no. 5, pp. 867–869, 1992.
  45. T. Starzynska, A. Wiechowska-Kozlowska, K. Marlicz et al., “5T4 oncofetal antigen in gastric carcinoma and its clinical significance,” European Journal of Gastroenterology and Hepatology, vol. 10, no. 6, pp. 479–484, 1998.
  46. C. J. Carsberg, K. A. Myers, and P. L. Stern, “Metastasis-associated 5T4 antigen disrupts cell-cell contacts and induces cellular motility in epithelial cells,” Molecular Biology of the Cell, vol. 7, p. 2275, 1996.
  47. L. E. Lindley and K. J. Briegel, “Molecular characterization of TGFβ-induced epithelial-mesenchymal transition in normal finite lifespan human mammary epithelial cells,” Biochemical and Biophysical Research Communications, vol. 399, no. 4, pp. 659–664, 2010. View at Publisher · View at Google Scholar · View at PubMed
  48. N. J. Sullivan, A. K. Sasser, A. E. Axel et al., “Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human breast cancer cells,” Oncogene, vol. 28, no. 33, pp. 2940–2947, 2009. View at Publisher · View at Google Scholar · View at PubMed
  49. H. Cheng, T. Fukushima, N. Takahashi, H. Tanaka, and H. Kataoka, “Hepatocyte growth factor activator inhibitor type 1 regulates epithelial to mesenchymal transition through membrane-bound serine proteinases,” Cancer Research, vol. 69, no. 5, pp. 1828–1835, 2009. View at Publisher · View at Google Scholar · View at PubMed
  50. Y. Yamauchi, T. Kohyama, H. Takizawa et al., “Tumor necrosis factor-α enhances both epithelial-mesenchymal transition and cell contraction induced in A549 human alveolar epithelial cells by transforming growth factor-β1,” Experimental Lung Research, vol. 36, no. 1, pp. 12–24, 2010. View at Publisher · View at Google Scholar · View at PubMed
  51. A. G. Smith, J. K. Heath, D. D. Donaldson et al., “Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides,” Nature, vol. 336, no. 6200, pp. 688–690, 1988.
  52. H. Niwa, K. Ogawa, D. Shimosato, and K. Adachi, “A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells,” Nature, vol. 460, no. 7251, pp. 118–122, 2009. View at Publisher · View at Google Scholar · View at PubMed
  53. N. R. D. Paling, H. Wheadon, H. K. Bone, and M. J. Welham, “Regulation of embryonic stem cell self-renewal by phosphoinositide 3-kinase-dependent signaling,” Journal of Biological Chemistry, vol. 279, no. 46, pp. 48063–48070, 2004. View at Publisher · View at Google Scholar · View at PubMed
  54. Q.-L. Ying, J. Nichols, I. Chambers, and A. Smith, “BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3,” Cell, vol. 115, no. 3, pp. 281–292, 2003. View at Publisher · View at Google Scholar
  55. Q.-L. Ying, J. Wray, J. Nichols et al., “The ground state of embryonic stem cell self-renewal,” Nature, vol. 453, no. 7194, pp. 519–523, 2008. View at Publisher · View at Google Scholar · View at PubMed
  56. F. Soncin, L. Mohamet, D. Eckardt et al., “Abrogation of E-cadherin-mediated cell-cell contact in mouse embryonic stem cells results in reversible LIF-independent self-renewal,” Stem Cells, vol. 27, no. 9, pp. 2069–2080, 2009. View at Publisher · View at Google Scholar · View at PubMed
  57. Q.-L. Ying, J. Wray, J. Nichols et al., “The ground state of embryonic stem cell self-renewal,” Nature, vol. 453, no. 7194, pp. 519–523, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  58. Y.-F. Chou, H.-H. Chen, M. Eijpe et al., “The growth factor environment defines distinct pluripotent ground states in novel blastocyst-derived stem cells,” Cell, vol. 135, no. 3, pp. 449–461, 2008. View at Publisher · View at Google Scholar · View at PubMed
  59. R. Arulanandam, A. Vultur, J. Cao et al., “Cadherin-cadherin engagement promotes cell survival via Rac1/Cdc42 and signal transducer and activator of transcription-3,” Molecular Cancer Research, vol. 7, no. 8, pp. 1310–1327, 2009. View at Publisher · View at Google Scholar · View at PubMed
  60. J. Massagué and Y.-G. Chen, “Controlling TGF-β signaling,” Genes and Development, vol. 14, no. 6, pp. 627–644, 2000.
  61. L. Vallier, S. Mendjan, S. Brown et al., “Activin/Nodal signalling maintains pluripotency by controlling Nanog expression,” Development, vol. 136, no. 8, pp. 1339–1349, 2009. View at Publisher · View at Google Scholar · View at PubMed
  62. L. Vallier, M. Alexander, and R. A. Pedersen, “Activin/Nodal and FGF pathways cooperate to maintain pluripotency of human embryonic stem cells,” Journal of Cell Science, vol. 118, no. 19, pp. 4495–4509, 2005. View at Publisher · View at Google Scholar · View at PubMed
  63. P. J. Tesar, J. G. Chenoweth, F. A. Brook et al., “New cell lines from mouse epiblast share defining features with human embryonic stem cells,” Nature, vol. 448, no. 7150, pp. 196–199, 2007. View at Publisher · View at Google Scholar · View at PubMed
  64. M. Nagaoka, U. Koshimizu, S. Yuasa et al., “E-cadherin-coated plates maintain pluripotent ES cells without colony formation,” PLoS ONE, vol. 1, no. 1, article e15, 2006. View at Publisher · View at Google Scholar · View at PubMed
  65. I.-M. Shih and M. Herlyn, “Role of growth factors and their receptors in the development and progression of melanoma,” Journal of Investigative Dermatology, vol. 100, no. 2, pp. 196S–203S, 1993.
  66. E. Lázár-Molnár, H. Hegyesi, S. Tóth, and A. Falus, “Autocrine and paracrine regulation by cytokines and growth factors in melanoma,” Cytokine, vol. 12, no. 6, pp. 547–554, 2000. View at Publisher · View at Google Scholar · View at PubMed
  67. E. Zwick, J. Bange, and A. Ullrich, “Receptor tyrosine kinase signalling as a target for cancer intervention strategies,” Endocrine-Related Cancer, vol. 8, no. 3, pp. 161–173, 2001. View at Publisher · View at Google Scholar
  68. S. R. Hubbard and W. T. Miller, “Receptor tyrosine kinases: mechanisms of activation and signaling,” Current Opinion in Cell Biology, vol. 19, no. 2, pp. 117–123, 2007. View at Publisher · View at Google Scholar · View at PubMed
  69. P. Blume-Jensen and T. Hunter, “Oncogenic kinase signalling,” Nature, vol. 411, no. 6835, pp. 355–365, 2001. View at Publisher · View at Google Scholar · View at PubMed
  70. R. Zandi, A. B. Larsen, P. Andersen, M.-T. Stockhausen, and H. S. Poulsen, “Mechanisms for oncogenic activation of the epidermal growth factor receptor,” Cellular Signalling, vol. 19, no. 10, pp. 2013–2023, 2007. View at Publisher · View at Google Scholar · View at PubMed
  71. G. L. Plosker and S. J. Keam, “Spotlight on trastuzumab in the management of HER2-positive metastatic and early-stage breast cancer,” BioDrugs, vol. 20, no. 4, pp. 259–262, 2006. View at Publisher · View at Google Scholar
  72. N. Normanno and W. J. Gullick, “Epidermal growth factor receptor tyrosine kinase inhibitors and bone metastases: different mechanisms of action for a novel therapeutic application?” Endocrine-Related Cancer, vol. 13, no. 1, pp. 3–6, 2006. View at Publisher · View at Google Scholar · View at PubMed
  73. X. Qian, T. Karpova, A. M. Sheppard, J. McNally, and D. R. Lowy, “E-cadherin-mediated adhesion inhibits ligand-dependent activation of diverse receptor tyrosine kinases,” The EMBO Journal, vol. 23, no. 8, pp. 1739–1748, 2004. View at Publisher · View at Google Scholar · View at PubMed
  74. M. Perrais, X. Chen, M. Perez-Moreno, and B. M. Gumbiner, “E-cadherin homophilic ligation inhibits cell growth and epidermal growth factor receptor signaling independently of other cell interactions,” Molecular Biology of the Cell, vol. 18, no. 6, pp. 2013–2025, 2007. View at Publisher · View at Google Scholar · View at PubMed
  75. C. D. Andl and A. K. Rustgi, “No one-way street: cross-talk between E-cadherin and receptor tyrosine kinase (RTK) signaling: a mechanism to regulate RTK activity,” Cancer Biology and Therapy, vol. 4, no. 1, pp. 28–31, 2005.
  76. A. Jeanes, C. J. Gottardi, and A. S. Yap, “Cadherins and cancer: how does cadherin dysfunction promote tumor progression?” Oncogene, vol. 27, no. 55, pp. 6920–6929, 2008. View at Publisher · View at Google Scholar · View at PubMed
  77. E. Seuntjens, L. Umans, A. Zwijsen, M. Sampaolesi, C. M. Verfaillie, and D. Huylebroeck, “Transforming Growth Factor type β and Smad family signaling in stem cell function,” Cytokine and Growth Factor Reviews, vol. 20, no. 5-6, pp. 449–458, 2009. View at Publisher · View at Google Scholar · View at PubMed
  78. P. Wikström, J.-E. Damber, and A. Bergh, “Role of transforming growth factor-β1 in prostate cancer,” Microscopy Research and Technique, vol. 52, no. 4, pp. 411–419, 2001. View at Publisher · View at Google Scholar
  79. B. A. Teicher, K. Menon, E. Alvarez, P. L. C. Shih, and M. M. Faul, “Antiangiogenic and antitumor effects of a protein kinase Cβ inhibitor in human hepatocellular and gastric cancer xenografts,” In Vivo, vol. 15, no. 3, pp. 185–193, 2001.
  80. J. A. Vrana, M. T. Stang, J. P. Grande, and M. J. Getz, “Expression of tissue factor in tumor stroma correlates with progression to invasive human breast cancer: paracrine regulation by carcinoma cell- derived members of the transforming growth factor β family,” Cancer Research, vol. 56, no. 21, pp. 5063–5070, 1996.
  81. C. Lee, S. M. Sintich, E. P. Mathews et al., “Transforming growth factor-β in benign and malignant prostate,” Prostate, vol. 39, no. 4, pp. 285–290, 1999. View at Publisher · View at Google Scholar
  82. J. Massagué and D. Wotton, “Transcriptional control by the TGF-β/Smad signaling system,” The EMBO Journal, vol. 19, no. 8, pp. 1745–1754, 2000.
  83. G. P. Risbridger, J. F. Schmitt, and D. M. Robertson, “Activins and inhibins in endocrine and other tumors,” Endocrine Reviews, vol. 22, no. 6, pp. 836–858, 2001. View at Publisher · View at Google Scholar
  84. K. A. Coerver, T. K. Woodruff, M. J. Finegold, J. Mather, A. Bradley, and M. M. Matzuk, “Activin signaling through activin receptor type II causes the cachexia-like symptoms in inhibin-deficient mice,” Molecular Endocrinology, vol. 10, no. 5, pp. 534–543, 1996.
  85. R. Halaban, B. S. Kwon, S. Ghosh, P. Delli Bovi, and A. Baird, “bFGF as an autocrine growth factor for human melanomas,” Oncogene Research, vol. 3, no. 2, pp. 177–186, 1988.
  86. Y. Wang and D. Becker, “Antisense targeting of basic fibroblast growth factor and fibroblast growth factor receptor-1 in human melanomas blocks intratumoral angiogenesis and tumor growth,” Nature Medicine, vol. 3, no. 8, pp. 887–893, 1997. View at Publisher · View at Google Scholar
  87. A. Huang and J. A. Wright, “Fibroblast growth factor mediated alterations in drug resistance, and evidence of gene amplification,” Oncogene, vol. 9, no. 2, pp. 491–499, 1994.
  88. J. Skarda, E. Fridman, P. Plevova et al., “Prognostic value of hMLH1 and hMSH2 immunohistochemical expression in non-small cell lung cancer. A tissue microarray study,” Biomedical papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia, vol. 150, no. 2, pp. 255–259, 2006.
  89. A. Miyake, M. Konishi, F. H. Martin et al., “Structure and expression of a novel member, FGF-16, of the fibroblast growth factor family,” Biochemical and Biophysical Research Communications, vol. 243, no. 1, pp. 148–152, 1998. View at Publisher · View at Google Scholar
  90. T. Ruotsalainen, H. Joensuu, K. Mattson, and P. Salven, “High pretreatment serum concentration of basic fibroblast growth factor is a predictor of poor prognosis in small cell lung cancer,” Cancer Epidemiology Biomarkers and Prevention, vol. 11, no. 11, pp. 1492–1495, 2002.
  91. A. M. Granato, O. Nanni, F. Falcini, et al., “Basic fibroblast growth factor and vascular endothelial growth factor serum levels in breast cancer patients and healthy women: useful as diagnostic tools?” Breast Cancer Research, vol. 6, pp. R38–R45, 2004.
  92. D. Giri, F. Ropiquet, and M. Ittmann, “Alterations in expression of basic fibroblast growth factor (FGF) 2 and its receptor FGFR-1 in human prostate cancer,” Clinical Cancer Research, vol. 5, no. 5, pp. 1063–1071, 1999.
  93. M. Amit, M. K. Carpenter, M. S. Inokuma et al., “Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture,” Developmental Biology, vol. 227, no. 2, pp. 271–278, 2000. View at Publisher · View at Google Scholar · View at PubMed
  94. S. Allerstorfer, G. Sonvilla, H. Fischer et al., “FGF5 as an oncogenic factor in human glioblastoma multiforme: autocrine and paracrine activities,” Oncogene, vol. 27, no. 30, pp. 4180–4190, 2008. View at Publisher · View at Google Scholar · View at PubMed
  95. H. J. Curtis, “Formal discussion of: somatic mutations and carcinogenesis,” Cancer Research, vol. 25, no. 8, pp. 1305–1308, 1965.
  96. L. A. Loeb, “A mutator phenotype in cancer,” Cancer Research, vol. 61, no. 8, pp. 3230–3239, 2001.
  97. B. Mintz and K. Illmensee, “Normal genetically mosaic mice produced from malignant teratocarcinoma cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 72, no. 9, pp. 3585–3589, 1975.
  98. J. Rossant and V. E. Papaioannou, “Outgrowth of embryonal carcinoma cells from injected blastocysts in vitro correlates with abnormal chimera development in vivo,” Experimental Cell Research, vol. 156, no. 1, pp. 213–220, 1985.
  99. C. Sonnenschein and A. M. Soto, “Theories of carcinogenesis: an emerging perspective,” Seminars in Cancer Biology, vol. 18, no. 5, pp. 372–377, 2008. View at Publisher · View at Google Scholar · View at PubMed
  100. C. Fey, “Virchow is opposition to the therapeutic nihilismus of his times,” Hippokrates, vol. 21, no. 23, pp. 679–681, 1950.
  101. K. Winter, “Significance of young Rudolf Virchow in present day thinking,” Zeitschrift für ärztliche Fortbildung, vol. 46, no. 18, pp. 522–530, 1952.
  102. G. B. Gruber, “When Virchow was a young physician,” Virchows Archiv, vol. 321, no. 5, pp. 462–481, 1952.
  103. S. S. WAIL, “Mechanical and anti-evolutionary conceptions of Virchow's cellularity and progress of pathology in the Soviet Union,” Sovetskaia Meditsina, vol. 8, pp. 6–11, 1950.
  104. T. Lapidot, C. Sirard, J. Vormoor et al., “A cell initiating human acute myeloid leukaemia after transplantation into SCID mice,” Nature, vol. 367, no. 6464, pp. 645–648, 1994. View at Publisher · View at Google Scholar · View at PubMed
  105. D. Bonnet and J. E. Dick, “Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell,” Nature Medicine, vol. 3, no. 7, pp. 730–737, 1997. View at Publisher · View at Google Scholar
  106. M. Al-Hajj, M. S. Wicha, A. Benito-Hernandez, S. J. Morrison, and M. F. Clarke, “Prospective identification of tumorigenic breast cancer cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 7, pp. 3983–3988, 2003. View at Publisher · View at Google Scholar · View at PubMed
  107. P. Zhang, H. Zuo, T. Ozaki, N. Nakagomi, and K. Kakudo, “Cancer stem cell hypothesis in thyroid cancer,” Pathology International, vol. 56, no. 9, pp. 485–489, 2006. View at Publisher · View at Google Scholar · View at PubMed
  108. C. Odoux, H. Fohrer, T. Hoppo et al., “A stochastic model for cancer stem cell origin in metastatic colon cancer,” Cancer Research, vol. 68, no. 17, pp. 6932–6941, 2008. View at Publisher · View at Google Scholar · View at PubMed
  109. M. F. Clarke, J. E. Dick, P. B. Dirks et al., “Cancer stem cells—perspectives on current status and future directions: AACR workshop on cancer stem cells,” Cancer Research, vol. 66, no. 19, pp. 9339–9344, 2006. View at Publisher · View at Google Scholar · View at PubMed
  110. P. N. Kelly, A. Dakic, J. M. Adams, S. L. Nutt, and A. Strasser, “Tumor growth need not be driven by rare cancer stem cells,” Science, vol. 317, no. 5836, p. 337, 2007. View at Publisher · View at Google Scholar · View at PubMed
  111. M.-H. Yoo and D. L. Hatfield, “The cancer stem Cell theory: is it correct?” Molecules and Cells, vol. 26, no. 5, pp. 514–516, 2008.
  112. S. A. Mani, W. Guo, M.-J. Liao et al., “The epithelial-mesenchymal transition generates cells with properties of stem cells,” Cell, vol. 133, no. 4, pp. 704–715, 2008. View at Publisher · View at Google Scholar · View at PubMed
  113. M. L. Hermiston, M. H. Wong, and J. I. Gordon, “Forced expression of E-cadherin in the mouse intestinal epithelium slows cell migration and provides evidence for nonautonomous regulation of cell fate in a self-renewing system,” Genes and Development, vol. 10, no. 8, pp. 985–996, 1996.
  114. L. Libusova, M. P. Stemmler, A. Hierholzer, H. Schwarz, and R. Kemler, “N-cadherin can structurally substitute for E-cadherin during intestinal development but leads to polyp formation,” Development, vol. 137, no. 14, pp. 2297–2305, 2010. View at Publisher · View at Google Scholar · View at PubMed
  115. L. Conti, S. M. Pollard, T. Gorba et al., “Niche-independent symmetrical self-renewal of a mammalian tissue stem cell,” PLoS Biology, vol. 3, no. 9, pp. 1594–1606, 2005. View at Publisher · View at Google Scholar · View at PubMed
  116. J. Stingl, P. Eirew, I. Ricketson et al., “Purification and unique properties of mammary epithelial stem cells,” Nature, vol. 439, no. 7079, pp. 993–997, 2006. View at Publisher · View at Google Scholar · View at PubMed
  117. A. A. G. Bryden, A. J. Freemont, N. W. Clarke, and N. J. R. George, “Paradoxical expression of E-cadherin in prostatic bone metastases,” BJU International, vol. 84, no. 9, pp. 1032–1034, 1999. View at Publisher · View at Google Scholar
  118. I. K. Bukholm, J. M. Nesland, and A.-L. Børresen-Dale, “Re-expression of E-cadherin, α-catenin and β-catenin, but not of γ- catenin, in metastatic tissue from breast cancer patients,” Journal of Pathology, vol. 190, no. 1, pp. 15–19, 2000.
  119. R. H. Gaspar, J. R. De los Toyos, C. A. Marcos, J. R. Riera, and A. Sampedro, “Quantitative immunohistochemical analyses of the expression of E- cadherin, thrombomodulin, CD44H and CD44v6 in primary tumours of pharynx/larynx squamous cell carcinoma and their lymph node metastases,” Analytical Cellular Pathology, vol. 18, no. 4, pp. 183–190, 1999.