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BioMed Research International
Volume 2014, Article ID 637308, 9 pages
http://dx.doi.org/10.1155/2014/637308
Review Article

E-Cadherin and Gastric Cancer: Cause, Consequence, and Applications

Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong

Received 13 March 2014; Revised 31 July 2014; Accepted 31 July 2014; Published 12 August 2014

Academic Editor: Valli De Re

Copyright © 2014 Xin Liu and Kent-Man Chu. 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. A. Jemal, F. Bray, M. M. Center, J. Ferlay, E. Ward, and D. Forman, “Global cancer statistics,” CA Cancer Journal for Clinicians, vol. 61, no. 2, pp. 69–90, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. C. D. Mathers and D. Loncar, “Projections of global mortality and burden of disease from 2002 to 2030,” PLoS Medicine, vol. 3, article e442, no. 11, 2006. View at Publisher · View at Google Scholar · View at Scopus
  3. J. Fléjou, “WHO Classification of digestive tumors: the fourth edition,” Annales de pathologie, vol. 31, no. 5, pp. S27–S31, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. C. Figueiredo, J. C. Machado, P. Pharoah et al., “Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma,” Journal of the National Cancer Institute, vol. 94, no. 22, pp. 1680–1687, 2002. View at Publisher · View at Google Scholar · View at Scopus
  5. B. Peleteiro, C. Lopes, C. Figueiredo, and N. Lunet, “Salt intake and gastric cancer risk according to Helicobacter pylori infection, smoking, tumour site and histological type,” British Journal of Cancer, vol. 104, no. 1, pp. 198–207, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. J. Paredes, J. Figueiredo, A. Albergaria et al., “Epithelial E- and P-cadherins: role and clinical significance in cancer,” Biochimica et Biophysica Acta—Reviews on Cancer, vol. 1826, no. 2, pp. 297–311, 2012. View at Publisher · View at Google Scholar · View at Scopus
  7. C. Caldas, F. Carneiro, H. T. Lynch et al., “Familial gastric cancer: overview and guidelines for management,” Journal of Medical Genetics, vol. 36, no. 12, pp. 873–880, 1999. View at Google Scholar · View at Scopus
  8. R. C. Fitzgerald, R. Hardwick, D. Huntsman et al., “Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research,” Journal of Medical Genetics, vol. 47, no. 7, pp. 436–444, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. M. J. G. Bussemakers, A. Van Bokhoven, M. Voller, F. P. Smit, and J. A. Schalken, “The genes for the calcium-dependent cell adhesion molecules P- and E-cadherin are tandemly arranged in the human genome,” Biochemical and Biophysical Research Communications, vol. 203, no. 2, pp. 1291–1294, 1994. View at Publisher · View at Google Scholar · View at Scopus
  10. 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 Scopus
  11. M. P. Stemmler, “Cadherins in development and cancer,” Molecular BioSystems, vol. 4, no. 8, pp. 835–850, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. M. Barber, A. Murrell, Y. Ito et al., “Mechanisms and sequelae of E-cadherin silencing in hereditary diffuse gastric cancer,” Journal of Pathology, vol. 216, no. 3, pp. 295–306, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. C. Oliveira, S. Sousa, H. Pinheiro et al., “Quantification of epigenetic and genetic 2nd hits in CDH1 during hereditary diffuse gastric cancer syndrome progression,” Gastroenterology, vol. 136, no. 7, pp. 2137–2148, 2009. View at Publisher · View at Google Scholar · View at Scopus
  14. S. Valastyan and R. A. Weinberg, “Tumor metastasis: molecular insights and evolving paradigms,” Cell, vol. 147, no. 2, pp. 275–292, 2011. View at Publisher · View at Google Scholar · View at Scopus
  15. K. Vleminckx, L. Vakaet Jr., M. Mareel, W. Fiers, and F. Van Roy, “Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role,” Cell, vol. 66, no. 1, pp. 107–119, 1991. View at Publisher · View at Google Scholar · View at Scopus
  16. T. M. H. Gall and A. E. Frampton, “Gene of the month: E-cadherin (CDH1),” Journal of Clinical Pathology, vol. 66, pp. 928–932, 2013. View at Publisher · View at Google Scholar · View at Scopus
  17. M. Takeichi, “Morphogenetic roles of classic cadherins,” Current Opinion in Cell Biology, vol. 7, no. 5, pp. 619–627, 1995. View at Publisher · View at Google Scholar · View at Scopus
  18. B. M. Gumbiner and P. D. McCrea, “Catenins as mediators of the cytoplasmic functions of cadherins,” Journal of Cell Science, Supplement, vol. 106, no. 17, pp. 155–158, 1993. View at Google Scholar · View at Scopus
  19. T. Yagi and M. Takeichi, “Cadherin superfamily genes: functions, genomic organization, and neurologic diversity,” Genes and Development, vol. 14, no. 10, pp. 1169–1180, 2000. View at Google Scholar · View at Scopus
  20. M. Ozawa, M. Ringwald, and R. Kemler, “Uvomorulin-catenin complex formation is regulated by a specific domain in the cytoplasmic region of the cell adhesion molecule,” Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 11, pp. 4246–4250, 1990. View at Publisher · View at Google Scholar · View at Scopus
  21. R. C. Ireton, M. A. Davis, J. van Hengel et al., “A novel role for p120 catenin in E-cadherin function,” Journal of Cell Biology, vol. 159, no. 3, pp. 465–476, 2002. View at Publisher · View at Google Scholar · View at Scopus
  22. 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 Publisher · View at Google Scholar · View at Scopus
  23. C. M. Niessen, D. Leckband, and A. S. Yap, “Tissue organization by cadherin adhesion molecules: dynamic molecular and cellular mechanisms of morphogenetic regulation,” Physiological Reviews, vol. 91, no. 2, pp. 691–731, 2011. View at Publisher · View at Google Scholar · View at Scopus
  24. A. García de Herreros and J. Baulida, “Cooperation, amplification, and feed-back in epithelial-mesenchymal transition,” Biochimica et Biophysica Acta: Reviews on Cancer, vol. 1825, no. 2, pp. 223–228, 2012. View at Publisher · View at Google Scholar · View at Scopus
  25. M. Katoh, “Epithelial-mesenchymal transition in gastric cancer (Review),” International Journal of Oncology, vol. 27, no. 6, pp. 1677–1683, 2005. View at Google Scholar · View at Scopus
  26. F. J. T. Staal, T. C. Luis, and M. M. Tiemessen, “WNT signalling in the immune system: WNT is spreading its wings,” Nature Reviews Immunology, vol. 8, no. 8, pp. 581–593, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. R. T. Moon, A. D. Kohn, G. V. de Ferrari, and A. Kaykas, “WNT and β-catenin signalling: diseases and therapies,” Nature Reviews Genetics, vol. 5, no. 9, pp. 691–701, 2004. View at Publisher · View at Google Scholar · View at Scopus
  28. C. J. Gottardi, E. Wong, and B. M. Gumbiner, “E-cadherin suppresses cellular transformation by inhibiting β-catenin signaling in an adhesion-independent manner,” Journal of Cell Biology, vol. 153, no. 5, pp. 1049–1060, 2001. View at Publisher · View at Google Scholar · View at Scopus
  29. E. Sahai and C. J. Marshall, “RHO - GTPases and cancer,” Nature Reviews Cancer, vol. 2, no. 2, pp. 133–142, 2002. View at Publisher · View at Google Scholar · View at Scopus
  30. Y. Pan, F. Bi, N. Liu et al., “Expression of seven main Rho family members in gastric carcinoma,” Biochemical and Biophysical Research Communications, vol. 315, no. 3, pp. 686–691, 2004. View at Publisher · View at Google Scholar · View at Scopus
  31. S. J. Heasman and A. J. Ridley, “Mammalian Rho GTPases: new insights into their functions from in vivo studies,” Nature Reviews Molecular Cell Biology, vol. 9, no. 9, pp. 690–701, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. G. Suriano, M. J. Oliveira, D. Huntsman et al., “E-cadherin germline missense mutations and cell phenotype: evidence for the independence of cell invasion on the motile capabilities of the cells,” Human Molecular Genetics, vol. 12, no. 22, pp. 3007–3016, 2003. View at Publisher · View at Google Scholar · View at Scopus
  33. A. Bremm, A. Walch, M. Fuchs et al., “Enhanced activation of epidermal growth factor receptor caused by tumor-derived E-cadherin mutations,” Cancer Research, vol. 68, no. 3, pp. 707–714, 2008. View at Publisher · View at Google Scholar · View at Scopus
  34. A. R. Mateus, R. Seruca, J. C. Machado et al., “EGFR regulates RhoA-GTP dependent cell motility in E-cadherin mutant cells,” Human Molecular Genetics, vol. 16, no. 13, pp. 1639–1647, 2007. View at Publisher · View at Google Scholar · View at Scopus
  35. E. Soto, M. Yanagisawa, L. A. Marlow, J. A. Copland, E. A. Perez, and P. Z. Anastasiadis, “p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression,” Journal of Cell Biology, vol. 183, no. 4, pp. 737–749, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. C. F. Cowell, I. K. Yan, T. Eiseler, A. C. Leightner, H. Döppler, and P. Storz, “Loss of cell-cell contacts induces NF-κB via RhoA-mediated activation of protein kinase D1,” Journal of Cellular Biochemistry, vol. 106, no. 4, pp. 714–728, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. M. Karin and F. R. Greten, “NF-κB: linking inflammation and immunity to cancer development and progression,” Nature Reviews Immunology, vol. 5, no. 10, pp. 749–759, 2005. View at Publisher · View at Google Scholar · View at Scopus
  38. Y. Ben-Neriah and M. Karin, “Inflammation meets cancer, with NF-κB as the matchmaker,” Nature Immunology, vol. 12, no. 8, pp. 715–723, 2011. View at Publisher · View at Google Scholar · View at Scopus
  39. S. Kuphal, I. Poser, C. Jobin, C. Hellerbrand, and A. K. Bosserhoff, “Loss of E-cadherin leads to upregulation of NFκB activity in malignant melanoma,” Oncogene, vol. 23, no. 52, pp. 8509–8519, 2004. View at Publisher · View at Google Scholar · View at Scopus
  40. G. Solanas, M. Porta-de-la-Riva, C. Agusti et al., “E-cadherin controls β-catenin and NF-κB transcriptional activity in mesenchymal gene expression,” Journal of Cell Science, vol. 121, no. 13, pp. 2224–2234, 2008. View at Publisher · View at Google Scholar · View at Scopus
  41. E. van Aken, O. de Wever, C. A. da Rocha, and M. Mareel, “Defective E-cadherin/catenin complexes in human cancer,” Virchows Archiv, vol. 439, no. 6, pp. 725–751, 2001. View at Publisher · View at Google Scholar · View at Scopus
  42. G. Berx and F. van Roy, “Involvement of members of the cadherin superfamily in cancer,” Cold Spring Harbor Perspectives in Biology, vol. 1, no. 6, Article ID a003129, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. K. Becker, M. J. Atkinson, U. Reich et al., “E-cadherin gene mutations provide clues to diffuse type gastric carcinomas,” Cancer Research, vol. 54, no. 14, pp. 3845–3852, 1994. View at Google Scholar · View at Scopus
  44. K. F. Becker and H. Hofler, “Frequent somatic allelic inactivation of the E-cadherin gene in gastric carcinomas,” Journal of the National Cancer Institute, vol. 87, no. 14, pp. 1082–1084, 1995. View at Publisher · View at Google Scholar · View at Scopus
  45. J. A. Efstathiou, D. Liu, J. M. D. Wheeler et al., “Mutated epithelial cadherin is associated with increased tumorigenicity and loss of adhesion and of responsiveness to the motogenic trefoil factor 2 in colon carcinoma cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 5, pp. 2316–2321, 1999. View at Publisher · View at Google Scholar · View at Scopus
  46. C. Huiping, J. R. Sigurgeirsdottir, J. G. Jonasson et al., “Chromosome alterations and E-cadherin gene mutations in human lobular breast cancer,” British Journal of Cancer, vol. 81, no. 7, pp. 1103–1110, 1999. View at Publisher · View at Google Scholar · View at Scopus
  47. G. Berx, A. Cleton-Jansen, K. Strumane et al., “E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain,” Oncogene, vol. 13, no. 9, pp. 1919–1925, 1996. View at Google Scholar · View at Scopus
  48. J. I. Risinger, A. Berchuck, M. F. Kohler, and J. Boyd, “Mutations of the E-cadherin gene in human gynecologic cancers,” Nature Genetics, vol. 7, no. 1, pp. 98–102, 1994. View at Publisher · View at Google Scholar · View at Scopus
  49. F. Carneiro, C. Oliveira, G. Suriano, and R. Seruca, “Molecular pathology of familial gastric cancer, with an emphasis on hereditary diffuse gastric cancer,” Journal of Clinical Pathology, vol. 61, no. 1, pp. 25–30, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. P. Guilford, J. Hopkins, J. Harraway et al., “E-cadherin germline mutations in familial gastric cancer,” Nature, vol. 392, no. 6674, pp. 402–405, 1998. View at Publisher · View at Google Scholar · View at Scopus
  51. C. Oliveira, P. Ferreira, S. Nabais et al., “E-Cadherin (CDH1) and p53 rather than SMAD4 and Caspase-10 germline mutations contribute to genetic predisposition in Portuguese gastric cancer patients,” European Journal of Cancer, vol. 40, no. 12, pp. 1897–1903, 2004. View at Publisher · View at Google Scholar · View at Scopus
  52. Y. Zhang, X. Liu, Y. Fan et al., “Germline mutations and polymorphic variants in MMR, E-cadherin and MYH genes associated with familial gastric cancer in Jiangsu of China,” International Journal of Cancer, vol. 119, no. 11, pp. 2592–2596, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. S. Nasri, H. More, F. Graziano et al., “A novel diffuse gastric cancer susceptibility variant in E-cadherin (CDH1) intron 2: a case control study in an Italian population,” BMC Cancer, vol. 8, article 138, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. S. Kim, J. W. Chung, T. D. Jeong et al., “Searching for E-cadherin gene mutations in early onset diffuse gastric cancer and hereditary diffuse gastric cancer in Korean patients,” Familial Cancer, vol. 12, no. 3, pp. 503–507, 2013. View at Publisher · View at Google Scholar · View at Scopus
  55. G. Strathdee, “Epigenetic versus genetic alterations in the inactivation of E-cadherin,” Seminars in Cancer Biology, vol. 12, no. 5, pp. 373–379, 2002. View at Publisher · View at Google Scholar · View at Scopus
  56. E. Yamamoto, H. Suzuki, H. Takamaru, H. Yamamoto, M. Toyota, and Y. Shinomura, “Role of DNA methylation in the development of diffuse-type gastric cancer,” Digestion, vol. 83, no. 4, pp. 241–249, 2011. View at Publisher · View at Google Scholar · View at Scopus
  57. N. R. Salama, M. L. Hartung, and A. Müller, “Life in the human stomach: persistence strategies of the bacterial pathogen Helicobacter pylori,” Nature Reviews Microbiology, vol. 11, no. 6, pp. 385–399, 2013. View at Publisher · View at Google Scholar · View at Scopus
  58. D. B. Polk and R. M. Peek Jr., “Helicobacter pylori: gastric cancer and beyond,” Nature Reviews Cancer, vol. 10, no. 6, pp. 403–414, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. F. Perri, R. Cotugno, A. Piepoli et al., “Aberrant DNA methylation in non-neoplastic gastric mucosa of H. pylori infected patients and effect of eradication,” The American Journal of Gastroenterology, vol. 102, no. 7, pp. 1361–1371, 2007. View at Publisher · View at Google Scholar · View at Scopus
  60. A. O. O. Chan, J. Z. Peng, S. K. Lam et al., “Eradication of Helicobacter pylori infection reverses E-cadherin promoter hypermethylation,” Gut, vol. 55, no. 4, pp. 463–468, 2006. View at Publisher · View at Google Scholar · View at Scopus
  61. A. O. Chan, B. C. Wong, H. Lan et al., “Deregulation of E-cadherin-catenin complex in precancerous lesions of gastric adenocarcinoma,” Journal of Gastroenterology and Hepatology, vol. 18, no. 5, pp. 534–539, 2003. View at Publisher · View at Google Scholar · View at Scopus
  62. A. O. Chan, S. Lam, B. C. Wong et al., “Promoter methylation of E-cadherin gene in gastric mucosa associated with Helicobacter pylori infection and in gastric cancer,” Gut, vol. 52, no. 4, pp. 502–506, 2003. View at Publisher · View at Google Scholar · View at Scopus
  63. J. M. David and A. K. Rajasekaran, “Dishonorable discharge: the oncogenic roles of cleaved E-cadherin fragments,” Cancer Research, vol. 72, no. 12, pp. 2917–2923, 2012. View at Publisher · View at Google Scholar · View at Scopus
  64. M. M. Grabowska and M. L. Day, “Soluble E-cadherin: More than a symptom of disease,” Frontiers in Bioscience, vol. 17, no. 5, pp. 1948–1964, 2012. View at Publisher · View at Google Scholar · View at Scopus
  65. M. Katayama, S. Hirai, K. Kamihagi, K. Nakagawa, M. Yasumoto, and I. Kato, “Soluble E-cadherin fragments increased in circulation of cancer patients,” British Journal of Cancer, vol. 69, no. 3, pp. 580–585, 1994. View at Publisher · View at Google Scholar · View at Scopus
  66. J. Gofuku, H. Shiozaki, Y. Doki et al., “Characterization of soluble E-cadherin as a disease marker in gastric cancer patients,” British Journal of Cancer, vol. 78, no. 8, pp. 1095–1101, 1998. View at Publisher · View at Google Scholar · View at Scopus
  67. O. de Wever, L. Derycke, A. Hendrix et al., “Soluble cadherins as cancer biomarkers,” Clinical and Experimental Metastasis, vol. 24, no. 8, pp. 685–697, 2007. View at Publisher · View at Google Scholar · View at Scopus
  68. A. O. Chan, S. K. Lam, K. M. Chu et al., “Soluble E-cadherin is a valid prognostic marker in gastric carcinoma,” Gut, vol. 48, no. 6, pp. 808–811, 2001. View at Publisher · View at Google Scholar · View at Scopus
  69. A. O. Chan, K. M. Chu, S. K. Lam et al., “Soluble E-cadherin is an independent pretherapeutic factor for long-term survival in gastric cancer,” Journal of Clinical Oncology, vol. 21, no. 12, pp. 2288–2293, 2003. View at Publisher · View at Google Scholar · View at Scopus
  70. A. O. O. Chan, K. Chu, S. K. Lam et al., “Early prediction of tumor recurrence after curative resection of gastric carcinoma by measuring soluble E-cadherin,” Cancer, vol. 104, no. 4, pp. 740–746, 2005. View at Publisher · View at Google Scholar · View at Scopus
  71. P. Guilford, B. Humar, and V. Blair, “Hereditary diffuse gastric cancer: translation of CDH1 germline mutations into clinical practice,” Gastric Cancer, vol. 13, no. 1, pp. 1–10, 2010. View at Publisher · View at Google Scholar · View at Scopus
  72. K. Miura, W. Fujibuchi, and I. Sasaki, “Alternative pre-mRNA splicing in digestive tract malignancy,” Cancer Science, vol. 102, no. 2, pp. 309–316, 2011. View at Publisher · View at Google Scholar · View at Scopus
  73. C. Oliveira, J. de Bruin, S. Nabais et al., “Intragenic deletion of CDH1 as the inactivating mechanism of the wild-type allele in an HDGC tumour,” Oncogene, vol. 23, no. 12, pp. 2236–2240, 2004. View at Publisher · View at Google Scholar · View at Scopus
  74. A. R. Brooks-Wilson, P. Kaurah, G. Suriano et al., “Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria,” Journal of Medical Genetics, vol. 41, no. 7, pp. 508–517, 2004. View at Publisher · View at Google Scholar · View at Scopus
  75. B. Mayrbaeurl, G. Keller, W. Schauer et al., “Germline mutation of the E-cadherin gene in three sibling cases with advanced gastric cancer: clinical consequences for the other family members,” European Journal of Gastroenterology and Hepatology, vol. 22, no. 3, pp. 306–310, 2010. View at Publisher · View at Google Scholar · View at Scopus
  76. F. M. Richards, S. A. McKee, M. H. Rajpar et al., “Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer,” Human Molecular Genetics, vol. 8, no. 4, pp. 607–610, 1999. View at Publisher · View at Google Scholar · View at Scopus
  77. T. P. McVeigh, J. K. Choi, N. M. Miller, A. J. Green, and M. J. Kerin, “Lobular breast cancer in a CDH1 splice site mutation carrier: case report and review of the literature,” Clinical Breast Cancer, vol. 14, no. 2, pp. e47–e51, 2014. View at Publisher · View at Google Scholar
  78. R. Kanasty, J. R. Dorkin, A. Vegas, and D. Anderson, “Delivery materials for siRNA therapeutics,” Nature Materials, vol. 12, pp. 967–977, 2013. View at Publisher · View at Google Scholar
  79. T. Martínez, N. Wright, M. López-Fraga, A. I. Jiménez, and C. Pañeda, “Silencing human genetic diseases with oligonucleotide-based therapies,” Human Genetics, vol. 132, no. 5, pp. 481–493, 2013. View at Publisher · View at Google Scholar · View at Scopus
  80. T. Tahara, T. Shibata, M. Nakamura et al., “Chronic aspirin use suppresses CDH1 methylation in human gastric mucosa,” Digestive Diseases and Sciences, vol. 55, no. 1, pp. 54–59, 2010. View at Publisher · View at Google Scholar · View at Scopus
  81. T. Tahara, T. Shibata, H. Yamashita et al., “Chronic nonsteroidal anti-inflammatory drug (NSAID) use suppresses multiple CpG islands hyper methylation (CIHM) of tumor suppressor genes in the human gastric mucosa,” Cancer Science, vol. 100, no. 7, pp. 1192–1197, 2009. View at Publisher · View at Google Scholar · View at Scopus
  82. J. K. Christman, “5-Azacytidine and 5-aza-2′-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy,” Oncogene, vol. 21, no. 35, pp. 5483–5495, 2002. View at Publisher · View at Google Scholar · View at Scopus
  83. R. L. Momparler, “Epigenetic therapy of cancer with 5-aza-2′-deoxycytidine (decitabine),” Seminars in Oncology, vol. 32, no. 5, pp. 443–451, 2005. View at Publisher · View at Google Scholar · View at Scopus
  84. C. Zhao and X. Bu, “Promoter methylation of tumorrelated genes in gastric carcinogenesis,” Histology and Histopathology, vol. 27, no. 10, pp. 1271–1282, 2012. View at Google Scholar · View at Scopus
  85. A. J. Murgo, “Innovative approaches to the clinical development of DNA methylation inhibitors as epigenetic remodeling drugs,” Seminars in Oncology, vol. 32, no. 5, pp. 458–464, 2005. View at Publisher · View at Google Scholar · View at Scopus
  86. G. Velikova, R. E. Banks, A. Gearing et al., “Circulating soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in patients with gastric cancer,” British Journal of Cancer, vol. 76, no. 11, pp. 1398–1404, 1997. View at Publisher · View at Google Scholar · View at Scopus
  87. M. Juhasz, M. P. A. Ebert, H. U. Schulz et al., “Dual role of serum soluble E-cadherin as a biological marker of metastatic development in gastric cancer,” Scandinavian Journal of Gastroenterology, vol. 38, no. 8, pp. 850–855, 2003. View at Publisher · View at Google Scholar · View at Scopus
  88. E. A. Miles, F. Thies, F. A. Wallace et al., “Influence of age and dietary fish oil on plasma soluble adhesion molecule concentrations,” Clinical Science, vol. 100, no. 1, pp. 91–100, 2001. View at Publisher · View at Google Scholar · View at Scopus
  89. C. Pedrazzani, S. Caruso, G. Corso et al., “Influence of age on soluble E-cadherin serum levels prevents its utility as a disease marker in gastric cancer patients,” Scandinavian Journal of Gastroenterology, vol. 43, no. 6, pp. 765–766, 2008. View at Publisher · View at Google Scholar · View at Scopus
  90. A. Jakubowska, M. Ławniczak, B. Wojnarska et al., “CDH1 gene mutations do not contribute in hereditary diffuse gastric cancer in Poland,” Familial Cancer, vol. 9, no. 4, pp. 605–608, 2010. View at Publisher · View at Google Scholar · View at Scopus
  91. C. G. Kleer, K. L. Van Golen, T. Braun, and S. D. Merajver, “Persistent E-cadherin expression in inflammatory breast cancer,” Modern Pathology, vol. 14, no. 5, pp. 458–464, 2001. View at Publisher · View at Google Scholar · View at Scopus
  92. M. R. Hoffmeyer, K. M. Wall, and S. F. Dharmawardhane, “In vitro analysis of the invasive phenotype of SUM 149, an inflammatory breast cancer cell line,” Cancer Cell International, vol. 5, article 11, 2005. View at Publisher · View at Google Scholar · View at Scopus
  93. N. Auersperg, J. Pan, B. D. Grove et al., “E-cadherin induces mesenchymal-to-epithelial transition in human ovarian surface epithelium,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 11, pp. 6249–6254, 1999. View at Publisher · View at Google Scholar · View at Scopus
  94. P. Reddy, L. Liu, C. Ren et al., “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,” Molecular Endocrinology, vol. 19, no. 10, pp. 2564–2578, 2005. View at Publisher · View at Google Scholar · View at Scopus
  95. F. J. Rodriguez, B. W. Scheithauer, C. Giannini, S. C. Bryant, and R. B. Jenkins, “Epithelial and pseudoepithelial differentiation in glioblastoma and gliosarcoma: a comparative morphologic and molecular genetic study,” Cancer, vol. 113, no. 10, pp. 2779–2789, 2008. View at Publisher · View at Google Scholar · View at Scopus
  96. L. J. Lewis-Tuffin, F. Rodriguez, C. Giannini et al., “Misregulated E-cadherin expression associated with an aggressive brain tumor phenotype,” PLoS ONE, vol. 5, no. 10, Article ID e13665, 2010. View at Publisher · View at Google Scholar · View at Scopus
  97. F. J. Rodriguez, L. J. Lewis-Tuffin, and P. Z. Anastasiadis, “E-cadherin's dark side: possible role in tumor progression,” Biochimica et Biophysica Acta: Reviews on Cancer, vol. 1826, no. 1, pp. 23–31, 2012. View at Publisher · View at Google Scholar · View at Scopus