Skip to main content
SpringerLink
Log in

Epigenetic Regulation of the E-Cadherin Cell-Cell Adhesion Gene

  • Chapter
DNA Methylation, Epigenetics and Metastasis

Part of the book series: Cancer Metastasis — Biology and Treatment ((CMBT,volume 7))

Abstract

Inactivation or loss of function of E-cadherin, the principal cell adhesion molecule in epithelial cells, is thought to be an important step in tumour progression and metastasis. In recent years, efforts have been made to understand how E-cadherin expression and function is regulated during these processes. Several mechanisms have been shown to be involved in the regulation of E-cadherin expression, including genetic, epigenetic and transcriptional changes. However, the complete picture of how this molecule is regulated still remains to be fully elucidated. As our understanding of how epigenetic mechanisms influence the control of gene expression expands it becomes clear that the epigenetic modification of genes involved in metastasis could influence the acquisition of malignant cell behaviour. In this chapter, we will focus our attention on the epigenetic control of the E-cadherin gene and discuss how this might be integrated with the known transcriptional repressors of E-cadherin. Understanding the epigenetic control of E-cadherin may help to identify new targets for drug design to block the metastatic process, the most aggressive and lethal consequence of tumour progression.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Liotta L.A., Kohn E.C. Cancer's deadly signature. Nat Genet, 2003; 33: 10–11.

    Article  PubMed  Google Scholar 

  2. Bogenrieder T., Herlyn M. Axis of evil: molecular mechanisms of cancer metastasis. Oncogene, 2003; 22: 6524–6536.

    Article  PubMed  Google Scholar 

  3. Thiery J.P. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer, 2002; 2: 442–454.

    Article  PubMed  Google Scholar 

  4. Thiery J.P. Epithelial-mesenchymal transitions in development and pathologies. Curr Opin Cell Biol, 2003; 15: 740–746.

    Article  PubMed  Google Scholar 

  5. Shook D., Keller R. Mechanisms, mechanics and function of epithelial-mesenchymal transitions in early development. Mech Dev, 2003; 120: 1351–1383.

    Article  PubMed  Google Scholar 

  6. Peinado H., Portillo F., Cano A. Transcriptional regulation of cadherins during development and carcinogenesis. Int J Dev Biol, 2004; 48: 365–375.

    Article  PubMed  Google Scholar 

  7. Takeichi M. The cadherins: cell-cell adhesion molecules controlling animal morphogenesis. Development, 1988; 102: 639–655.

    PubMed  Google Scholar 

  8. Takeichi M. Morphogenetic roles of classic cadherins. Curr Opin Cell Biol, 1995; 7: 619–627.

    Article  PubMed  Google Scholar 

  9. Larue L., Antos C., Butz S., Huber O., Delmas V., Dominis M., Kemler R. A role for cadherins in tissue formation. Development, 1996; 122: 3185–3194.

    PubMed  Google Scholar 

  10. Birchmeier W., Behrens J. Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta, 1994; 1198: 11–26.

    PubMed  Google Scholar 

  11. Takeichi M. Cadherins in cancer: implications for invasion and metastasis. Curr Opin Cell Biol, 1993; 5: 806–811.

    Article  PubMed  Google Scholar 

  12. Christofori G., Semb H. The role of the cell-adhesion molecule E-cadherin as a tumour-suppressor gene. Trends Biochem Sci, 1999; 24: 73–76.

    Article  PubMed  Google Scholar 

  13. Mansouri A., Spurr N., Goodfellow P.N., Kemler R. Characterization and chromosomal localization of the gene encoding the human cell adhesion molecule uvomorulin. Differentiation, 1988; 38: 67–71.

    PubMed  Google Scholar 

  14. Eistetter H.R., Adolph S., Ringwald M., Simon-Chazottes D., Schuh R., Guenet J.L., Kemler R. Chromosomal mapping of the structural gene coding for the mouse cell adhesion molecule uvomorulin. Proc Natl Acad Sci U S A, 1988; 85: 3489–3493.

    PubMed  Google Scholar 

  15. Berx G., Becker K.F., Hofler H., van Roy F. Mutations of the human E-cadherin (CDH1) gene. Hum Mutat, 1998; 12: 226–237.

    Article  PubMed  Google Scholar 

  16. Strathdee G. Epigenetic versus genetic alterations in the inactivation of E-cadherin. Semin Cancer Biol, 2002; 12: 373–379.

    Article  PubMed  Google Scholar 

  17. Berx G., Cleton-Jansen A.M., Nollet F., de Leeuw W.J., van de Vijver M., Cornelisse C., van Roy F. E-cadherin is a tumour/invasion suppressor gene mutated in human lobular breast cancers. EMBO J, 1995; 14: 6107–6115.

    PubMed  Google Scholar 

  18. Berx G., Cleton-Jansen A.M., Strumane K., de Leeuw W.J., Nollet F., van Roy F., Cornelisse C. E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain. Oncogene, 1996; 13: 1919–1925.

    PubMed  Google Scholar 

  19. Vos C.B., Cleton-Jansen A.M., Berx G., de Leeuw W.J., ter Haar N.T., van Roy F., Cornelisse C.J., Peterse J.L., van de Vijver M.J. E-cadherin inactivation in lobular carcinoma in situ of the breast: an early event in tumorigenesis. Br J Cancer, 1997; 76: 1131–1133.

    PubMed  Google Scholar 

  20. Moll R., Mitze M., Frixen U.H., Birchmeier W. Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas. Am J Pathol, 1993; 143: 1731–1742.

    PubMed  Google Scholar 

  21. Gamallo C., Palacios J., Suarez A., Pizarro A., Navarro P., Quintanilla M., Cano A. Correlation of E-cadherin expression with differentiation grade and histological type in breast carcinoma. Am J Pathol, 1993; 142: 987–993.

    PubMed  Google Scholar 

  22. Machado J.C., Soares P., Carneiro F., Rocha A., Beck S., Blin N., Berx G., Sobrinho-Simoes M. E-cadherin gene mutations provide a genetic basis for the phenotypic divergence of mixed gastric carcinomas. Lab Invest, 1999; 79: 459–465.

    PubMed  Google Scholar 

  23. Guilford P., Hopkins J., Harraway J., McLeod M., McLeod N., Harawira P., Taite H., Scoular R., Miller A., Reeve A.E. E-cadherin germline mutations in familial gastric cancer. Nature, 1998; 392: 402–405.

    Article  PubMed  Google Scholar 

  24. Becker K.F., Atkinson M.J., Reich U., Becker I., Nekarda H., Siewert J.R., Hofler H. Ecadherin gene mutations provide clues to diffuse type gastric carcinomas. Cancer Res, 1994; 54: 3845–3852.

    PubMed  Google Scholar 

  25. Grady W.M., Willis J., Guilford P.J., Dunbier A.K., Toro T.T., Lynch H., Wiesner G., Ferguson K., Eng C., Park J.G., Kim S.J., Markowitz S. Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer. Nat Genet 2000; 26: 16–17.

    Article  PubMed  Google Scholar 

  26. Cheng C.W., Wu P.E., Yu J.C., Huang C.S., Yue C.T., Wu C.W., Shen C.Y., Mechanisms of inactivation of E-cadherin in breast carcinoma: modification of the two-hit hypothesis of tumor suppressor gene. Oncogene, 2001; 3814–3823.

    Google Scholar 

  27. Machado J.C., Oliveira C., Carvalho R., Soares P., Berx G., Caldas C., Seruca R., Carneiro F., Sobrinho-Simoes M. E-cadherin gene (CDH1) promoter methylation as the second hit in sporadic diffuse gastric carcinoma. Oncogene, 2001; 20: 1525–1528.

    Article  PubMed  Google Scholar 

  28. Tamura G., Yin J., Wang S., Fleisher A.S., Zou T., Abraham J.M., Kong D., Smolinski K.N., Wilson K.T., James S.P., Silverberg S.G., Nishizuka S., Terashima M., Motoyama T., Meltzer S.J. E-Cadherin gene promoter hypermethylation in primary human gastric carcinomas. J Natl Cancer Inst, 2000; 92: 569–573.

    Article  PubMed  Google Scholar 

  29. Feinberg A.P., Tycko B. The history of cancer epigenetics. Nat Rev Cancer, 2004; 4: 143–153.

    Article  PubMed  Google Scholar 

  30. Yoshiura K., Kanai Y., Ochiai A., Shimoyama Y., Sugimura T., Hirohashi S. Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc Natl Acad Sci U S A, 1995; 92: 7416–7419.

    PubMed  Google Scholar 

  31. Graff J.R., Herman J.G., Lapidus R.G., Chopra H., Xu R., Jarrard D.F., Isaacs W.B., Pitha P.M., Davidson N.E., Baylin S.B. E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. Cancer Res, 1995; 55: 5195–5199.

    PubMed  Google Scholar 

  32. Graziano F., Humar B., Guilford P. The role of the E-cadherin gene (CDH1) in diffuse gastric cancer susceptibility: from the laboratory to clinical practice. Ann Oncol, 2003; 14: 1705–1713.

    Article  PubMed  Google Scholar 

  33. Graziano F., Arduini F., Ruzzo A., Mandolesi A., Bearzi I., Silva R., Muretto P., Testa E., Mari D., Magnani M., Scartozzi M., Cascinu S. Combined analysis of E-cadherin gene (CDH1) promoter hypermethylation and E-cadherin protein expression in patients with gastric cancer: implications for treatment with demethylating drugs. Ann Oncol, 2004; 15: 489–492.

    Article  PubMed  Google Scholar 

  34. Graziano F., Arduini F., Ruzzo A., Bearzi I., Humar B., More H., Silva R., Muretto P., Guilford P., Testa E., Mari D., Magnani M., Cascinu S. Prognostic analysis of E-cadherin gene promoter hypermethylation in patients with surgically resected, node-positive, diffuse gastric cancer. Clin Cancer Res, 2004; 10: 2784–2789.

    Article  PubMed  Google Scholar 

  35. Ichikawa D., Koike H., Ikoma H., Ikoma D., Tani N., Otsuji E., Kitamura K., Yamagishi H. Detection of aberrant methylation as a tumor marker in serum of patients with gastric cancer. Anticancer Res, 2004; 24: 2477–2481.

    PubMed  Google Scholar 

  36. Lee T.L., Leung W.K., Chan M.W., Ng E.K., Tong J.H., Lo K.W., Chung S.C., Sung J.J., To K.F. Detection of gene promoter hypermethylation in the tumor and serum of patients with gastric carcinoma. Clin Cancer Res, 2002; 8: 1761–1766.

    PubMed  Google Scholar 

  37. House M.G., Guo M., Efron D.T., Lillemoe K.D., Cameron J.L., Syphard J.E., Hooker C.M., Abraham S.C., Montgomery E.A., Herman J.G., Brock M.V. Tumor suppressor gene hypermethylation as a predictor of gastric stromal tumor behavior. J Gastrointest Surg, 2003; 7: 1004–1014.

    Article  PubMed  Google Scholar 

  38. Concolino P., Papa V., Mozzetti S., Ferlini C., Pacelli F., Martinelli E., Ricci R., Filippetti F., Scambia G., Doglietto G.B. The unsolved enigma of CDH1 down-regulation in hereditary diffuse gastric cancer. J Surg Res, 2004; 121: 50–55.

    Article  PubMed  Google Scholar 

  39. Ebert M.P., Yu J., Hoffmann J., Rocco A., Rocken C., Kahmann S., Muller O., Korc M., Sung J.J., Malfertheiner P. Loss of beta-catenin expression in metastatic gastric cancer. J Clin Oncol, 2003; 21: 1708–1714.

    Article  PubMed  Google Scholar 

  40. Mielnicki L.M., Asch H.L., Asch B.B. Genes, chromatin, and breast cancer: an epigenetic tale. J Mammary Gland Biol Neoplasia, 2001; 6: 169–182.

    Article  PubMed  Google Scholar 

  41. Nass S.J., Herman J.G., Gabrielson E., Iversen P.W., Parl F.F., Davidson N.E., Graff J.R. Aberrant methylation of the estrogen receptor and E-cadherin 5′ CpG islands increases with malignant progression in human breast cancer. Cancer Res, 2000; 60: 4346–4348.

    PubMed  Google Scholar 

  42. Droufakou S., Deshmane V., Roylance R., Hanby A., Tomlinson I., Hart I.R. Multiple ways of silencing E-cadherin gene expression in lobular carcinoma of the breast. Int J Cancer, 2001; 92: 404–408.

    Article  PubMed  Google Scholar 

  43. Hajra K.M., Ji X., Fearon E.R. Extinction of E-cadherin expression in breast cancer via a dominant repression pathway acting on proximal promoter elements. Oncogene, 1999; 18: 7274–7279.

    Article  PubMed  Google Scholar 

  44. Li L.C., Chui R.M., Sasaki M., Nakajima K., Perinchery G., Au H.C., Nojima D., Carroll P., Dahiya R. A single nucleotide polymorphism in the E-cadherin gene promoter alters transcriptional activities. Cancer Res, 2000; 60: 873–876.

    PubMed  Google Scholar 

  45. Sarrio D., Moreno-Bueno G., Hardisson D., Sanchez-Estevez C., Guo M., Herman J.G., Gamallo C., Esteller M., Palacios J. Epigenetic and genetic alterations of APC and CDH1 genes in lobular breast cancer: relationships with abnormal E-cadherin and catenin expression and microsatellite instability. Int J Cancer, 2003; 106: 208–215.

    Article  PubMed  Google Scholar 

  46. Brown A.M. Wnt signaling in breast cancer: have we come full circle? Breast Cancer Res, 2001; 3: 351–355.

    Article  PubMed  Google Scholar 

  47. Berx G., Van Roy F. The E-cadherin/catenin complex: an important gatekeeper in breast cancer tumorigenesis and malignant progression. Breast Cancer Res 2001; 3: 289–293.

    Article  PubMed  Google Scholar 

  48. Yang S.Z., Kohno N., Yokoyama A., Kondo K., Hamada H., Hiwada K. Decreased E-cadherin augments beta-catenin nuclear localization: studies in breast cancer cell lines. Int J Oncol, 2001; 18: 541–548.

    PubMed  Google Scholar 

  49. van de Wetering M., Barker N., Harkes I.C., van der Heyden M., Dijk N.J., Hollestelle A., Klijn J.G., Clevers H., Schutte M. Mutant E-cadherin breast cancer cells do not display constitutive Wnt signaling. Cancer Res, 2001; 61: 278–284.

    PubMed  Google Scholar 

  50. Medeiros A.C., Nagai M.A., Neto M.M., Brentani R.R. Loss of heterozygosity affecting the APC and MCC genetic loci in patients with primary breast carcinomas. Cancer Epidemiol Biomarkers Prev, 1994; 3: 331–333.

    PubMed  Google Scholar 

  51. Jin Z., Tamura G., Tsuchiya T., Sakata K., Kashiwaba M., Osakabe M., Motoyama T. Adenomatous polyposis coli (APC) gene promoter hypermethylation in primary breast cancers. Br J Cancer, 2001; 85: 69–73.

    Article  PubMed  Google Scholar 

  52. Zheng Z., Pan J., Chu B., Wong Y.C., Cheung A.L., Tsao S.W. Down-regulation and abnormal expression of E-cadherin and beta-catenin in nasopharyngeal carcinoma: close association with advanced disease stage and lymph node metastasis. Hum Pathol, 1999; 30: 458–466.

    Article  PubMed  Google Scholar 

  53. Washington K., Chiappori A., Hamilton K., Shyr Y., Blanke C., Johnson D., Sawyers J., Beauchamp D. Expression of beta-catenin, alpha-catenin, and E-cadherin in Barrett's esophagus and esophageal adenocarcinomas. Mod Pathol, 1998; 11: 805–813.

    PubMed  Google Scholar 

  54. Nakanishi Y., Ochiai A., Akimoto S., Kato H., Watanabe H., Tachimori Y., Yamamoto S., Hirohashi S. Expression of E-cadherin, alpha-catenin, beta-catenin and plakoglobin in esophageal carcinomas and its prognostic significance: immunohistochemical analysis of 96 lesions. Oncology, 1997; 54: 158–165.

    PubMed  Google Scholar 

  55. Si H.X., Tsao S.W., Lam K.Y., Srivastava G., Liu Y., Wong Y.C., Shen Z.Y., Cheung A.L. E-cadherin expression is commonly downregulated by CpG island hypermethylation in esophageal carcinoma cells. Cancer Lett, 2001; 173: 71–78.

    Article  PubMed  Google Scholar 

  56. Takeno S., Noguchi T., Fumoto S., Kimura Y., Shibata T., Kawahara K. E-cadherin expression in patients with esophageal squamous cell carcinoma: promoter hypermethylation, Snail overexpression, and clinicopathologic implications. Am J Clin Pathol, 2004; 122: 78–84.

    Article  PubMed  Google Scholar 

  57. Eads C.A., Lord R.V., Kurumboor S.K., Wickramasinghe K., Skinner M.L., Long T.I., Peters J.H., DeMeester T.R., Danenberg K.D., Danenberg P.V., Laird P.W., Skinner K.A. Fields of aberrant CpG island hypermethylation in Barrett's esophagus and associated adenocarcinoma. Cancer Res, 2000; 60: 5021–5026.

    PubMed  Google Scholar 

  58. Corn P.G., Heath E.I., Heitmiller R., Fogt F., Forastiere A.A., Herman J.G., Wu T.T. Frequent hypermethylation of the 5′ CpG island of E-cadherin in esophageal adenocarcinoma. Clin Cancer Res, 2001; 7: 2765–2769.

    PubMed  Google Scholar 

  59. Brock M.V., Gou M., Akiyama Y., Muller A., Wu T.T., Montgomery E., Deasel M., Germonpre P., Rubinson L., Heitmiller R.F., Yang S.C., Forastiere A.A., Baylin S.B., Herman J.G. Prognostic importance of promoter hypermethylation of multiple genes in esophageal adenocarcinoma. Clin Cancer Res, 2003; 9: 2912–2919.

    PubMed  Google Scholar 

  60. Li L.C., Zhao H., Nakajima K., Oh B.R., Filho L.A., Carroll P., Dahiya R. Methylation of the E-cadherin gene promoter correlates with progression of prostate cancer. J Urol, 2001; 166: 705–709.

    Article  PubMed  Google Scholar 

  61. Singal R., Ferdinand L., Reis I.M., Schlesselman J.J. Methylation of multiple genes in prostate cancer and the relationship with clinicopathological features of disease. Oncol Rep, 2004; 12: 631–637.

    PubMed  Google Scholar 

  62. Kallakury B.V., Sheehan C.E., Winn-Deen E., Oliver J., Fisher H.A., Kaufman R.P., Jr., Ross J.S. Decreased expression of catenins (alpha and beta), p120 CTN, and Ecadherin cell adhesion proteins and E-cadherin gene promoter methylation in prostatic adenocarcinomas. Cancer, 2001; 92: 2786–2795.

    Article  PubMed  Google Scholar 

  63. Ribeiro-Filho L.A., Franks J., Sasaki M., Shiina H., Li L.C., Nojima D., Arap S., Carroll P., Enokida H., Nakagawa M., Yonezawa S., Dahiya R. CpG hypermethylation of promoter region and inactivation of E-cadherin gene in human bladder cancer. Mol Carcinog, 2002; 34: 187–198.

    PubMed  Google Scholar 

  64. Horikawa Y., Sugano K., Shigyo M., Yamamoto H., Nakazono M., Fujimoto H., Kanai Y., Hirohashi S., Kakizoe T., Habuchi T., Kato T. Hypermethylation of an E-cadherin (CDH1) promoter region in high grade transitional cell carcinoma of the bladder comprising carcinoma in situ. J Urol, 2003; 169: 1541–1545.

    Article  PubMed  Google Scholar 

  65. Thievessen I., Seifert H.H., Swiatkowski S., Florl A.R., Schulz W.A. E-cadherin involved in inactivation of WNT/beta-catenin signalling in urothelial carcinoma and normal urothelial cells. Br J Cancer, 2003; 88: 1932–1938.

    Article  PubMed  Google Scholar 

  66. Nigam A.K., Savage F.J., Boulos P.B., Stamp G.W., Liu D., Pignatelli M. Loss of cell-cell and cell-matrix adhesion molecules in colorectal cancer. Br J Cancer, 1993; 68: 507–514.

    PubMed  Google Scholar 

  67. Dorudi S., Sheffield J.P., Poulsom R., Northover J.M., Hart I.R. E-cadherin expression in colorectal cancer. An immunocytochemical and in situ hybridization study. Am J Pathol, 1993; 142: 981–986.

    PubMed  Google Scholar 

  68. Kinsella A.R., Lepts G.C., Hill C.L., Jones M. Reduced E-cadherin expression correlates with increased invasiveness in colorectal carcinoma cell lines. Clin Exp Metastasis, 1994; 12: 335–342.

    Article  PubMed  Google Scholar 

  69. Efstathiou J.A., Liu D., Wheeler J.M.D., Kim H.C., Beck N.E., Ilyas M., Karayiannakis A.J., Mortensen N.J.M., Kmiot W., Playford R.J., Pignatelli M., Bodmer W.F. 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. Proc Natl Acad Sci U S A, 1999; 96: 2316–2321.

    Article  PubMed  Google Scholar 

  70. Wheeler J.M., Kim H.C., Efstathiou J.A., Ilyas M., Mortensen N.J., Bodmer W.F. Hypermethylation of the promoter region of the E-cadherin gene (CDH1) in sporadic and ulcerative colitis associated colorectal cancer. Gut 2001; 48: 367–371.

    Article  PubMed  Google Scholar 

  71. Garinis G.A., Menounos P.G., Spanakis N.E., Papadopoulos K., Karavitis G., Parassi I., Christeli E., Patrinos G.P., Manolis E.N., Peros G. Hypermethylation-associated transcriptional silencing of E-cadherin in primary sporadic colorectal carcinomas. J Pathol, 2002; 198: 442–449.

    Article  PubMed  Google Scholar 

  72. Kanazawa T., Watanabe T., Kazama S., Tada T., Koketsu S., Nagawa H. Poorly differentiated adenocarcinoma and mucinous carcinoma of the colon and rectum show higher rates of loss of heterozygosity and loss of E-cadherin expression due to methylation of promoter region. Int J Cancer, 2002; 102: 225–229.

    Article  PubMed  Google Scholar 

  73. Kanazawa N., Oda T., Gunji N., Nozue M., Kawamoto T., Todoroki T., Fukao K. Ecadherin expression in the primary tumors and metastatic lymph nodes of poorly differentiated types of rectal cancer. Surg Today, 2002; 32: 123–128.

    Article  PubMed  Google Scholar 

  74. Lin S.Y., Yeh K.T., Chen W.T., Chen H.C., Chen S.T., Chiou H.Y., Chang J.G. Promoter CpG methylation of tumor suppressor genes in colorectal cancer and its relationship to clinical features. Oncol Rep, 2004; 11: 341–348.

    PubMed  Google Scholar 

  75. Wong N.A.C.S., Pignatelli M. Beta-catenin-A Linchpin in Colorectal Carcinogenesis? Am J Pathol, 2002; 160: 389–401.

    PubMed  Google Scholar 

  76. Garinis G.A., Spanakis N.E., Menounos P.G., Manolis E.N., Peros G. Transcriptional impairment of beta-catenin/E-cadherin complex is not associated with beta-catenin mutations in colorectal carcinomas. Br J Cancer 2003; 88: 206–209.

    Article  PubMed  Google Scholar 

  77. Esteller M., Sparks A., Toyota M., Sanchez-Cespedes M., Capella G., Peinado M.A., Gonzalez S., Tarafa G., Sidransky D., Meltzer S.J., Baylin S.B., Herman J.G. Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer. Cancer Res, 2000; 60: 4366–4371.

    PubMed  Google Scholar 

  78. Young J., Biden K.G., Simms L.A., Huggard P., Karamatic R., Eyre H.J., Sutherland G.R., Herath N., Barker M., Anderson G.J., Fitzpatrick D.R., Ramm G.A., Jass J.R., Leggett B.A. HPP1: a transmembrane protein-encoding gene commonly methylated in colorectal polyps and cancers. Proc Natl Acad Sci U S A, 2001; 98: 265–270.

    Article  PubMed  Google Scholar 

  79. Toyooka S., Toyooka K.O., Harada K., Miyajima K., Makarla P., Sathyanarayana U.G., Yin J., Sato F., Shivapurkar N., Meltzer S.J., Gazdar A.F. Aberrant methylation of the CDH13 (H-cadherin) promoter region in colorectal cancers and adenomas. Cancer Res, 2002; 62: 3382–3386.

    PubMed  Google Scholar 

  80. Hibi K., Nakayama H., Kodera Y., Ito K., Akiyama S., Nakao A. CDH13 promoter region is specifically methylated in poorly differentiated colorectal cancer. Br J Cancer, 2004; 90: 1030–1033.

    Article  PubMed  Google Scholar 

  81. Toyooka S., Toyooka K.O., Maruyama R., Virmani A.K., Girard L., Miyajima K., Harada K., Ariyoshi Y., Takahashi T., Sugio K., Brambilla E., Gilcrease M., Minna J.D., Gazdar A.F. DNA methylation profiles of lung tumors. Mol Cancer Ther, 2001; 1: 61–67.

    PubMed  Google Scholar 

  82. Shimamoto T., Ohyashiki J.H., Hirano T., Kato H., Ohyashiki K. Hypermethylation of E-cadherin gene is frequent and independent of p16INK4A methylation in non-small cell lung cancer: potential prognostic implication. Oncol Rep, 2004; 12: 389–395.

    PubMed  Google Scholar 

  83. Toyooka K.O., Toyooka S., Virmani A.K., Sathyanarayana U.G., Euhus D.M., Gilcrease M., Minna J.D., Gazdar A.F. Loss of expression and aberrant methylation of the CDH13 (H-cadherin) gene in breast and lung carcinomas. Cancer Res, 2001; 61: 4556–4560.

    PubMed  Google Scholar 

  84. Sato M., Mori Y., Sakurada A., Fujimura S., Horii A. The H-cadherin (CDH13) gene is inactivated in human lung cancer. Hum Genet, 1998; 103: 96–101.

    Article  PubMed  Google Scholar 

  85. Kanai Y., Ushijima S., Tsuda H., Sakamoto M., Sugimura T., Hirohashi S. Aberrant DNA methylation on chromosome 16 is an early event in hepatocarcinogenesis. Jpn J Cancer Res, 1996; 87: 1210–1217.

    PubMed  Google Scholar 

  86. Kanai Y., Ushijima S., Hui A.M., Ochiai A., Tsuda H., Sakamoto M., Hirohashi S. The E-cadherin gene is silenced by CpG methylation in human hepatocellular carcinomas. Int J Cancer, 1997; 71: 355–359.

    Article  PubMed  Google Scholar 

  87. Kanai Y., Ushijima S., Tsuda H., Sakamoto M., Hirohashi S. Aberrant DNA methylation precedes loss of heterozygosity on chromosome 16 in chronic hepatitis and liver cirrhosis. Cancer Lett 2000; 148: 73–80.

    Article  PubMed  Google Scholar 

  88. Matsumura T., Makino R., Mitamura K. Frequent down-regulation of E-cadherin by genetic and epigenetic changes in the malignant progression of hepatocellular carcinomas. Clin Cancer Res, 2001; 7: 594–599.

    PubMed  Google Scholar 

  89. Calvisi D.F., Ladu S., Conner E.A., Factor V.M., Thorgeirsson S.S. Disregulation of E-cadherin in transgenic mouse models of liver cancer. Lab Invest, 2004; 84: 1137–1147.

    Article  PubMed  Google Scholar 

  90. Dulaimi E., De C., II, Uzzo R.G., Al-Saleem T., Greenberg R.E., Polascik T.J., Babb J.S., Grizzle W.E., Cairns P. Promoter hypermethylation profile of kidney cancer. Clin Cancer Res, 2004; 10: 3972–3979.

    Article  PubMed  Google Scholar 

  91. Nojima D., Nakajima K., Li L.C., Franks J., Ribeiro-Filho L., Ishii N., Dahiya R. CpG methylation of promoter region inactivates E-cadherin gene in renal cell carcinoma. Mol Carcinog, 2001; 32: 19–27.

    Article  PubMed  Google Scholar 

  92. Chen C.L., Liu S.S., Ip S.M., Wong L.C., Ng T.Y., Ngan H.Y. E-cadherin expression is silenced by DNA methylation in cervical cancer cell lines and tumours. Eur J Cancer, 2003; 39: 517–523.

    Article  PubMed  Google Scholar 

  93. Narayan G., Arias-Pulido H., Koul S., Vargas H., Zhang F.F., Villella J., Schneider A., Terry M.B., Mansukhani M., Murty V.V. Frequent promoter methylation of CDH1, DAPK, RARB, and HIC1 genes in carcinoma of cervix uteri: its relationship to clinical outcome. Mol Cancer, 2003; 2: 24.

    Article  PubMed  Google Scholar 

  94. Widschwendter A., Ivarsson L., Blassnig A., Muller H.M., Fiegl H., Wiedemair A., Muller-Holzner E., Goebel G., Marth C., Widschwendter M. CDH1 and CDH13 methylation in serum is an independent prognostic marker in cervical cancer patients. Int J Cancer, 2004; 109: 163–166.

    Article  PubMed  Google Scholar 

  95. Saito T., Nishimura M., Yamasaki H., Kudo R. Hypermethylation in promoter region of E-cadherin gene is associated with tumor dedifferention and myometrial invasion in endometrial carcinoma. Cancer, 2003; 97: 1002–1009.

    Article  PubMed  Google Scholar 

  96. Moreno-Bueno G., Hardisson D., Sanchez C., Sarrio D., Cassia R., Garcia-Rostan G., Prat J., Guo M., Herman J.G., Matias-Guiu X., Esteller M., Palacios J. Abnormalities of the APC/beta-catenin pathway in endometrial cancer. Oncogene, 2002; 21: 7981–7990.

    Article  PubMed  Google Scholar 

  97. Moreno-Bueno G., Rodriguez-Perales S., Sanchez-Estevez C., Marcos R., Hardisson D., Cigudosa J.C., Palacios J. Molecular alterations associated with cyclin D1 overexpression in endometrial cancer. Int J Cancer, 2004; 110: 194–200.

    Article  PubMed  Google Scholar 

  98. Chiles M.C., Ai L., Zuo C., Fan C.Y., Smoller B.R. E-cadherin promoter hypermethylation in preneoplastic and neoplastic skin lesions. Mod Pathol, 2003; 16: 1014–1018.

    Article  PubMed  Google Scholar 

  99. Fraga M.F., Herranz M., Espada J., Ballestar E., Paz M.F., Ropero S., Erkek E., Bozdogan O., Peinado H., Niveleau A., Mao J.H., Balmain A., Cano A., Esteller M. A mouse skin multistage carcinogenesis model reflects the aberrant DNA methylation patterns of human tumors. Cancer Res, 2004; 64: 5527–5534.

    Article  PubMed  Google Scholar 

  100. Takeuchi T., Liang S.B., Matsuyoshi N., Zhou S., Miyachi Y., Sonobe H., Ohtsuki Y. Loss of T-cadherin (CDH13, H-cadherin) expression in cutaneous squamous cell carcinoma. Lab Invest, 2002; 82: 1023–1029.

    PubMed  Google Scholar 

  101. Takeuchi T., Liang S.B., Ohtsuki Y. Down-regulation of expression of a novel cadherin molecule, T-cadherin, in basal cell carcinoma of the skin. Mol Carcinog, 2002; 35: 173–179.

    Article  PubMed  Google Scholar 

  102. Saito Y., Takazawa H., Uzawa K., Tanzawa H., Sato K. Reduced expression of Ecadherin in oral squamous cell carcinoma: relationship with DNA methylation of 5′ CpG island. Int J Oncol, 1998; 12: 293–298.

    PubMed  Google Scholar 

  103. Nakayama S., Sasaki A., Mese H., Alcalde R.E., Tsuji T., Matsumura T. The Ecadherin gene is silenced by CpG methylation in human oral squamous cell carcinomas. Int J Cancer 2001; 93: 667–673.

    Article  PubMed  Google Scholar 

  104. Chang H.W., Chow V., Lam K.Y., Wei W.I., Yuen A. Loss of E-cadherin expression resulting from promoter hypermethylation in oral tongue carcinoma and its prognostic significance. Cancer, 2002; 94: 386–392.

    Article  PubMed  Google Scholar 

  105. Hazan R.B., Qiao R., Keren R., Badano I., Suyama K. Cadherin switch in tumor progression. Ann N Y Acad Sci, 2004; 1014: 155–163.

    Article  PubMed  Google Scholar 

  106. Chen Q., Lipkina G., Song Q., Kramer R.H. Promoter methylation regulates cadherin switching in squamous cell carcinoma. Biochem Biophys Res Commun, 2004; 315: 850–856.

    Article  PubMed  Google Scholar 

  107. Kudo Y., Kitajima S., Ogawa I., Hiraoka M., Sargolzaei S., Keikhaee M.R., Sato S., Miyauchi M., Takata T. Invasion and metastasis of oral cancer cells require methylation of E-cadherin and/or degradation of membranous beta-catenin. Clin Cancer Res, 2004; 10: 5455–5463.

    Article  PubMed  Google Scholar 

  108. Melki J.R., Vincent P.C., Brown R.D., Clark S.J. Hypermethylation of E-cadherin in leukemia. Blood, 2000; 95: 3208–3213.

    PubMed  Google Scholar 

  109. Farinha N.J., Shaker S., Lemaire M., Momparler L., Bernstein M., Momparler R.L. Activation of expression of p15, p73 and E-cadherin in leukemic cells by different concentrations of 5-aza-2′-deoxycytidine (Decitabine). Anticancer Res, 2004; 24: 75–78.

    PubMed  Google Scholar 

  110. Corn P.G., Smith B.D., Ruckdeschel E.S., Douglas D., Baylin S.B., Herman J.G. E-cadherin expression is silenced by 5′ CpG island methylation in acute leukemia. Clin Cancer Res, 2000; 6: 4243–4248.

    PubMed  Google Scholar 

  111. Seidl S., Ackermann J., Kaufmann H., Keck A., Nosslinger T., Zielinski C.C., Drach J., Zochbauer-Muller S. DNA-methylation analysis identifies the E-cadherin gene as a potential marker of disease progression in patients with monoclonal gammopathies. Cancer, 2004; 100: 2598–2606.

    Article  PubMed  Google Scholar 

  112. Galm O., Wilop S., Reichelt J., Jost E., Gehbauer G., Herman J.G., Osieka R. DNA methylation changes in multiple myeloma. Leukemia, 2004; 18: 1687–1692.

    Article  PubMed  Google Scholar 

  113. Roman-Gomez J., Castillejo J.A., Jimenez A., Cervantes F., Boque C., Hermosin L., Leon A., Granena A., Colomer D., Heiniger A., Torres A. Cadherin-13, a mediator of calcium-dependent cell-cell adhesion, is silenced by methylation in chronic myeloid leukemia and correlates with pretreatment risk profile and cytogenetic response to interferon alfa. J Clin Oncol, 2003; 21: 1472–1479.

    Article  PubMed  Google Scholar 

  114. Behrens J., Lowrick O., Klein-Hitpass L., Birchmeier W. The E-cadherin promoter: functional analysis of a G.C-rich region and an epithelial cell-specific palindromic regulatory element. Proc Natl Acad Sci U S A, 1991; 88: 11495–11499.

    PubMed  Google Scholar 

  115. Faraldo M.L., Rodrigo I., Behrens J., Birchmeier W., Cano A. Analysis of the E-cadherin and P-cadherin promoters in murine keratinocyte cell lines from different stages of mouse skin carcinogenesis. Mol Carcinog, 1997; 20: 33–47.

    Article  PubMed  Google Scholar 

  116. Hennig G., Lowrick O., Birchmeier W., Behrens J. Mechanisms identified in the transcriptional control of epithelial gene expression. J Biol Chem 1996; 271: 595–602.

    Article  PubMed  Google Scholar 

  117. Rodrigo I., Cato A.C., 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: 358–371.

    Article  PubMed  Google Scholar 

  118. Comijn J., Berx G., Vermassen P., Verschueren K., van Grunsven L., Bruyneel E., Mareel M., Huylebroeck D., van Roy F. The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell, 2001; 7: 1267–1278.

    Article  PubMed  Google Scholar 

  119. Batlle E., Sancho E., Franci C., Dominguez D., Monfar M., Baulida J., Garcia De Herreros A. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol, 2000; 2: 84–89.

    Article  PubMed  Google Scholar 

  120. Hajra K.M., Chen D.Y., Fearon E.R. The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Res, 2002; 62: 1613–1618.

    PubMed  Google Scholar 

  121. Cano A., Perez-Moreno M.A., Rodrigo I., Locascio A., Blanco M.J., del Barrio M.G., Portillo F., Nieto M.A. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol, 2000; 2: 76–83.

    Article  PubMed  Google Scholar 

  122. Bolós V., Peinado H., Perez-Moreno M.A., Fraga M.F., Esteller M., Cano A. The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. J Cell Sci, 2003; 116: 499–511.

    Article  PubMed  Google Scholar 

  123. Pérez-Moreno M.A., Locascio A., Rodrigo I., Dhondt G., Portillo F., Nieto M.A., Cano A. A new role for E12/E47 in the repression of E-cadherin expression and epithelial-mesenchymal transitions. J Biol Chem, 2001; 276: 27424–27431.

    Article  PubMed  Google Scholar 

  124. Yang J., Mani S.A., Donaher J.L., Ramaswamy S., Itzykson R.A., Come C., Savagner P., Gitelman I., Richardson A., Weinberg R.A. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell, 2004; 117: 927–939.

    Article  PubMed  Google Scholar 

  125. Grooteclaes M.L., Frisch S.M. Evidence for a function of CtBP in epithelial gene regulation and anoikis. Oncogene, 2000; 19: 3823–3828.

    Article  PubMed  Google Scholar 

  126. Blanco M.J., Moreno-Bueno G., Sarrio D., Locascio A., Cano A., Palacios J., Nieto M.A. Correlation of Snail expression with histological grade and lymph node status in breast carcinomas. Oncogene, 2002; 21: 3241–3246.

    Article  PubMed  Google Scholar 

  127. Cheng C.W., Wu P.E., Yu J.C., Huang C.S., Yue C.T., Wu C.W., Shen C.Y. Mechanisms of inactivation of E-cadherin in breast carcinoma: modification of the two-hit hypothesis of tumor suppressor gene. Oncogene, 2001; 20: 3814–3823.

    Article  PubMed  Google Scholar 

  128. Sugimachi K., Tanaka S., Kameyama T., Taguchi K., Aishima S., Shimada M., Tsuneyoshi M. Transcriptional repressor snail and progression of human hepatocellular carcinoma. Clin Cancer Res, 2003; 9: 2657–2664.

    PubMed  Google Scholar 

  129. Guaita S., Puig I., Franci C., Garrido M., Dominguez D., Batlle E., Sancho E., Dedhar S., De Herreros A.G., Baulida J. Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression. J Biol Chem, 2002; 277: 39209–39216.

    Article  PubMed  Google Scholar 

  130. Rosivatz E., Becker I., Specht K., Fricke E., Luber B., Busch R., Hofler H., Becker K.F. Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer. Am J Pathol, 2002; 161: 1881–1891.

    PubMed  Google Scholar 

  131. Nieto M.A. The snail superfamily of zinc-finger transcription factors. Nat Rev Mol Cell Biol, 2002; 3: 155–166.

    Article  PubMed  Google Scholar 

  132. van de Putte T., Maruhashi M., Francis A., Nelles L., Kondoh H., Huylebroeck D., Higashi Y. Mice lacking ZFHX1B, the gene that codes for Smad-interacting protein-1, reveal a role for multiple neural crest cell defects in the etiology of Hirschsprung disease-mental retardation syndrome. Am J Hum Genet, 2003; 72: 465–470.

    Article  PubMed  Google Scholar 

  133. Bukholm I.K., Nesland J.M., Borresen-Dale A.L. Re-expression of E-cadherin, alpha-catenin and beta-catenin, but not of gamma-catenin, in metastatic tissue from breast cancer patients. J Pathol, 2000; 190: 15–19.

    Article  PubMed  Google Scholar 

  134. Gamallo C., Palacios, J., Benito, N., Limeres, M.A., Pizarro, A., Suarez, A., Pastrana, F., Cano, A., Calero, F. Expression of E-cadherin in 230 infiltrating ductal breast carcinoma: Relationship to clinicopathological features. Int J Oncology, 1996; 9: 1207–1212.

    Google Scholar 

  135. Mareel M.M., Behrens J., Birchmeier W., De Bruyne G.K., Vleminckx K., Hoogewijs A., Fiers W.C., Van Roy F.M. Down-regulation of E-cadherin expression in Madin Darby canine kidney (MDCK) cells inside tumors of nude mice. Int J Cancer, 1991; 47: 922–928.

    PubMed  Google Scholar 

  136. Behrens J., Frixen U., Schipper J., Weidner M., Birchmeier W. Cell adhesion in invasion and metastasis. Semin Cell Biol, 1992; 3: 169–178.

    PubMed  Google Scholar 

  137. Mareel M., Bracke M., Van Roy F., Vakaet L. Expression of E-cadherin in embryogenetic ingression and cancer invasion. Int J Dev Biol, 1993; 37: 227–235.

    PubMed  Google Scholar 

  138. Graff J.R., Gabrielson E., Fujii H., Baylin S.B., Herman J.G. Methylation patterns of the E-cadherin 5′ CpG island are unstable and reflect the dynamic, heterogeneous loss of E-cadherin expression during metastatic progression. J Biol Chem 2000; 275: 2727–2732.

    Article  PubMed  Google Scholar 

  139. Bird A.P., Wolffe A.P. Methylation-induced repression—belts, braces, and chromatin. Cell, 1999; 99: 451–454.

    Article  PubMed  Google Scholar 

  140. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev 2002; 16: 6–21.

    Article  PubMed  Google Scholar 

  141. Fournier C., Goto Y., Ballestar E., Delaval K., Hever A.M., Esteller M., Feil R. Allele-specific histone lysine methylation marks regulatory regions at imprinted mouse genes. EMBO J, 2002; 21: 6560–6570.

    Article  PubMed  Google Scholar 

  142. Peinado H., Ballestar E., Esteller M., Cano A. Snail Mediates E-Cadherin Repression by the Recruitment of the Sin3A/Histone Deacetylase 1 (HDAC1)/HDAC2 Complex. Mol Cell Biol, 2004; 24: 306–319.

    Article  PubMed  Google Scholar 

  143. Shi Y., Sawada J., Sui G., Affar el B., Whetstine J.R., Lan F., Ogawa H., Luke M.P., Nakatani Y. Coordinated histone modifications mediated by a CtBP co-repressor complex. Nature, 2003; 422: 735–738.

    Article  PubMed  Google Scholar 

  144. El-Osta A., Wolffe A.P. DNA methylation and histone deacetylation in the control of gene expression: basic biochemistry to human development and disease. Gene Expr, 2000; 9: 63–75.

    PubMed  Google Scholar 

  145. Hemavathy K., Ashraf S.I., Ip Y.T. Snail/slug family of repressors: slowly going into the fast lane of development and cancer. Gene, 2000; 257: 1–12.

    Article  PubMed  Google Scholar 

  146. Fujita N., Jaye D.L., Kajita M., Geigerman C., Moreno C.S., Wade P.A. MTA3, a Mi-2/NuRD Complex Subunit, Regulates an Invasive Growth Pathway in Breast Cancer. Cell, 2003; 113: 207–219.

    Article  PubMed  Google Scholar 

  147. Noma K., Allis C.D., Grewal S.I. Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries. Science, 2001; 293: 1150–1155.

    Article  PubMed  Google Scholar 

  148. Koizume S., Tachibana K., Sekiya T., Hirohashi S., Shiraishi M. Heterogeneity in the modification and involvement of chromatin components of the CpG island of the silenced human CDH1 gene in cancer cells. Nucleic Acids Res 2002; 30: 4770–4780.

    Article  PubMed  Google Scholar 

  149. Bestor T.H. The DNA methyltransferases of mammals. Hum Mol Genet, 2000; 9: 2395–2402.

    Article  PubMed  Google Scholar 

  150. El-Osta A. DNMT cooperativity—the developing links between methylation, chromatin structure and cancer. Bioessays, 2003; 25: 1071–1084.

    Article  PubMed  Google Scholar 

  151. Graff J.R., Herman J.G., Myohanen S., Baylin S.B., Vertino P.M. Mapping patterns of CpG island methylation in normal and neoplastic cells implicates both upstream and downstream regions in de novo methylation. J Biol Chem, 1997; 272: 22322–22329.

    Article  PubMed  Google Scholar 

  152. Girault I., Tozlu S., Lidereau R., Bieche I. Expression analysis of DNA methyltransferases 1, 3A, and 3B in sporadic breast carcinomas. Clin Cancer Res, 2003; 9: 4415–4422.

    PubMed  Google Scholar 

  153. Etoh T., Kanai Y., Ushijima S., Nakagawa T., Nakanishi Y., Sasako M., Kitano S., Hirohashi S. Increased DNA methyltransferase 1 (DNMT1) protein expression correlates significantly with poorer tumor differentiation and frequent DNA hypermethylation of multiple CpG islands in gastric cancers. Am J Pathol, 2004; 164: 689–699.

    PubMed  Google Scholar 

  154. Kawasaki H., Taira K. Induction of DNA methylation and gene silencing by short interfering RNAs in human cells. Nature, 2004; 431: 211–217.

    Article  PubMed  Google Scholar 

  155. Fujita N., Takebayashi S., Okumura K., Kudo S., Chiba T., Saya H., Nakao M. Methylation-Mediated Transcriptional Silencing in Euchromatin by Methyl-CpG Binding Protein MBD1 Isoforms. Mol Cell Biol, 1999; 19: 6415–6426.

    PubMed  Google Scholar 

  156. Darwanto A., Kitazawa R., Maeda S., Kitazawa S. MeCP2 and promoter methylation cooperatively regulate E-cadherin gene expression in colorectal carcinoma. Cancer Sci, 2003; 94: 442–447.

    Article  PubMed  Google Scholar 

  157. Nan X., Ng H.H., Johnson C.A., Laherty C.D., Turner B.M., Eisenman R.N., Bird A. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature, 1998; 393: 386–389.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departamento de Bioquímica, Facultad de Medicina, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC-UAM, Madrid, Spain

    Héctor Peinado & Amparo Cano

Authors
  1. Héctor Peinado
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amparo Cano
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Spanish National Cancer Centre (CNIO), Madrid, Spain

    Manel Esteller

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer

About this chapter

Cite this chapter

Peinado, H., Cano, A. (2005). Epigenetic Regulation of the E-Cadherin Cell-Cell Adhesion Gene. In: Esteller, M. (eds) DNA Methylation, Epigenetics and Metastasis. Cancer Metastasis — Biology and Treatment, vol 7. Springer, Dordrecht. https://doi.org/10.1007/1-4020-3642-6_7

Download citation

Publish with us

Policies and ethics

Search

Navigation