Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular and Clinical Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 2049-9450 Online ISSN: 2049-9469
Journal Cover
January-February 2013 Volume 1 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
January-February 2013 Volume 1 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review

Epigenetic control of epithelial-mesenchymal-transition in human cancer (Review)

  • Authors:
    • Tobias Kiesslich
    • Martin Pichler
    • Daniel Neureiter
  • View Affiliations / Copyright

    Affiliations: Institute of Pathology, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg, Austria, Division of Oncology, Department of Internal Medicine, Medical University of Graz (MUG), Graz, Austria
  • Pages: 3-11
    |
    Published online on: September 25, 2012
       https://doi.org/10.3892/mco.2012.28
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Development and tissue homeostasis as well as carcinogenesis share the evolutionary conserved process of epithelial-mesenchymal transition (EMT). EMT enables differentiated epithelial cells to trans-differentiate to a mesenchymal phenotype which is associated with diverse cellular properties including altered morphology, migration and invasion and stemness. In physiological development and tissue homeostasis, EMT exerts beneficial functions for structured tissue formation and maintenance. Under pathological conditions, EMT causes uncontrolled tissue repair and organ fibrosis, as well as the induction of tumor growth, angiogenesis and metastasis in the context of cancer progression. Particularly, the metastatic process is essentially linked to diverse EMT-driven functions which give the mesenchymal differentiated tumor cells the capacity to migrate and form micrometastases in distant organs. Recent analyses of the mechanisms controlling EMT revealed a significant epigenetic regulatory impact reflecting the reversible nature of EMTs. As several approaches of epigenetic therapy are already under clinical evaluation, including inhibitors of DNA methyl transferase and histone deacetylase, targeting the epigenetic regulation of EMT may represent a promising therapeutic option in the future. Therefore, we undertook this review to reassess the current knowledge on the roles of epigenetic control in the regulation of EMT in human cancer. These recent findings are discussed in view of their implications on future diagnostic and therapeutic strategies.
View Figures

Figure 1

Figure 2

Figure 3

View References

1. 

Thiery JP and Sleeman JP: Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 7:131–142. 2006.

2. 

Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelialmesenchymal transitions in development and disease. Cell. 139:871–890. 2009.

3. 

Hugo H, Ackland ML, Blick T, Lawrence MG, Clements JA, Williams ED and Thompson EW: Epithelial - mesenchymal and mesenchymal - epithelial transitions in carcinoma progression. J Cell Physiol. 213:374–383. 2007.

4. 

Choi SS and Diehl AM: Epithelial-to-mesenchymal transitions in the liver. Hepatology. 50:2007–2013. 2009.

5. 

Brabletz T, Jung A, Spaderna S, Hlubek F and Kirchner T: Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression. Nat Rev Cancer. 5:744–749. 2005.

6. 

Kiesslich T, Berr F, Alinger B, Kemmerling R, Pichler M, Ocker M and Neureiter D: Current status of therapeutic targeting of developmental signalling pathways in oncology. Curr Pharm Biotechnol. 13:2184–2220. 2012.

7. 

Kirchner T and Brabletz T: Patterning and nuclear beta-catenin expression in the colonic adenoma-carcinoma sequence. Analogies with embryonic gastrulation. Am J Pathol. 157:1113–1121. 2000.

8. 

Brabletz T: To differentiate or not - routes towards metastasis. Nat Rev Cancer. 12:425–436. 2012.

9. 

Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–1428. 2009.

10. 

Guarino M, Rubino B and Ballabio G: The role of epithelial-mesenchymal transition in cancer pathology. Pathology. 39:305–318. 2007.

11. 

Moustakas A and Heldin CH: Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci. 98:1512–1520. 2007.

12. 

Voulgari A and Pintzas A: Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta. 1796:75–90. 2009.

13. 

Scheel C and Weinberg RA: Cancer stem cells and epithelialmesenchymal transition: Concepts and molecular links. Semin Cancer Biol. Apr 23–2012, (E-pub ahead of print).

14. 

McConkey DJ, Choi W, Marquis L, et al: Role of epithelial-to-mesenchymal transition (EMT) in drug sensitivity and metastasis in bladder cancer. Cancer Metastasis Rev. 28:335–344. 2009.

15. 

Ouyang G, Wang Z, Fang X, Liu J and Yang CJ: Molecular signaling of the epithelial to mesenchymal transition in generating and maintaining cancer stem cells. Cell Mol Life Sci. 67:2605–2618. 2010.

16. 

Moll R, Divo M and Langbein L: The human keratins: biology and pathology. Histochem Cell Biol. 129:705–733. 2008.

17. 

Frixen UH, Behrens J, Sachs M, et al: E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol. 113:173–185. 1991.

18. 

Onder TT, Gupta PB, Mani SA, Yang J, Lander ES and Weinberg RA: Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res. 68:3645–3654. 2008.

19. 

Perl AK, Wilgenbus P, Dahl U, Semb H and Christofori G: A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature. 392:190–193. 1998.

20. 

Schipper JH, Frixen UH, Behrens J, Unger A, Jahnke K and Birchmeier W: E-cadherin expression in squamous cell carcinomas of head and neck: inverse correlation with tumor dedifferentiation and lymph node metastasis. Cancer Res. 51:6328–6337. 1991.

21. 

Umbas R, Isaacs WB, Bringuier PP, et al: Decreased E-cadherin expression is associated with poor prognosis in patients with prostate cancer. Cancer Res. 54:3929–3933. 1994.

22. 

Cavallaro U, Schaffhauser B and Christofori G: Cadherins and the tumour progression: is it all in a switch? Cancer Lett. 176:123–128. 2002.

23. 

Maeda M, Johnson KR and Wheelock MJ: Cadherin switching: essential for behavioral but not morphological changes during an epithelium-to-mesenchyme transition. J Cell Sci. 118:873–887. 2005.

24. 

Gregory PA, Bert AG, Paterson EL, et al: The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 10:593–601. 2008.

25. 

Park SM, Gaur AB, Lengyel E and Peter ME: The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 22:894–907. 2008.

26. 

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

27. 

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

28. 

Bolos V, Peinado H, Perez-Moreno MA, Fraga MF, Esteller M and 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. 116:499–511. 2003.

29. 

Grooteclaes ML and Frisch SM: Evidence for a function of CtBP in epithelial gene regulation and anoikis. Oncogene. 19:3823–3828. 2000.

30. 

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

31. 

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

32. 

Nakaya Y and Sheng G: Epithelial to mesenchymal transition during gastrulation: an embryological view. Dev Growth Differ. 50:755–766. 2008.

33. 

Qin Q, Xu Y, He T, Qin C and Xu J: Normal and disease-related biological functions of Twist1 and underlying molecular mechanisms. Cell Res. 22:90–106. 2012.

34. 

Piera-Velazquez S, Li Z and Jimenez SA: Role of endothelial-mesenchymal transition (EndoMT) in the pathogenesis of fibrotic disorders. Am J Pathol. 179:1074–1080. 2011.

35. 

Hanahan D and Weinberg RA: Hallmarks of cancer: the next generation. Cell. 144:646–674. 2011.

36. 

Hanahan D and Weinberg RA: The hallmarks of cancer. Cell. 100:57–70. 2000.

37. 

Chaffer CL, Thompson EW and Williams ED: Mesenchymal to epithelial transition in development and disease. Cells Tissues Organs. 185:7–19. 2007.

38. 

Yang J and Weinberg RA: Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 14:818–829. 2008.

39. 

Neureiter D, Herold C and Ocker M: Gastrointestinal cancer - only a deregulation of stem cell differentiation? (Review). Int J Mol Med. 17:483–489. 2006.

40. 

Zeisberg M, Yang C, Martino M, Duncan MB, Rieder F, Tanjore H and Kalluri R: Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition. J Biol Chem. 282:23337–23347. 2007.

41. 

Kim KK, Kugler MC, Wolters PJ, et al: Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proc Natl Acad Sci USA. 103:13180–13185. 2006.

42. 

Zeisberg EM, Tarnavski O, Zeisberg M, et al: Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat Med. 13:952–961. 2007.

43. 

Zeisberg EM, Potenta SE, Sugimoto H, Zeisberg M and Kalluri R: Fibroblasts in kidney fibrosis emerge via endothelial-to-mesenchymal transition. J Am Soc Nephrol. 19:2282–2287. 2008.

44. 

Yanez-Mo M, Lara-Pezzi E, Selgas R, et al: Peritoneal dialysis and epithelial-to-mesenchymal transition of mesothelial cells. N Engl J Med. 348:403–413. 2003.

45. 

Stintzing S, Ocker M, Hartner A, Amann K, Barbera L and Neureiter D: Differentiation patterning of vascular smooth muscle cells (VSMC) in atherosclerosis. Virchows Arch. 455:171–185. 2009.

46. 

Saika S, Ikeda K, Yamanaka O, et al: Transient adenoviral gene transfer of Smad7 prevents injury-induced epithelial-mesenchymal transition of lens epithelium in mice. Lab Invest. 84:1259–1270. 2004.

47. 

Tan X, Li Y and Liu Y: Paricalcitol attenuates renal interstitial fibrosis in obstructive nephropathy. J Am Soc Nephrol. 17:3382–3393. 2006.

48. 

Zeisberg M, Bottiglio C, Kumar N, Maeshima Y, Strutz F, Muller GA and Kalluri R: Bone morphogenic protein-7 inhibits progression of chronic renal fibrosis associated with two genetic mouse models. Am J Physiol Renal Physiol. 285:F1060–F1067. 2003.

49. 

Jung A, Brabletz T and Kirchner T: The migrating cancer stem cells model - a conceptual explanation of malignant tumour progression. Ernst Schering Found Symp Proc. 109–124. 2006.

50. 

Handra-Luca A, Hong SM, Walter K, Wolfgang C, Hruban R and Goggins M: Tumour epithelial vimentin expression and outcome of pancreatic ductal adenocarcinomas. Br J Cancer. 104:1296–1302. 2011.

51. 

Hong SM, Li A, Olino K, et al: Loss of E-cadherin expression and outcome among patients with resectable pancreatic adenocarcinomas. Mod Pathol. 24:1237–1247. 2011.

52. 

Jouppila-Matto A, Tuhkanen H, Soini Y, et al: Transcription factor snail1 expression and poor survival in pharyngeal squamous cell carcinoma. Histol Histopathol. 26:443–449. 2011.

53. 

Franci C, Gallen M, Alameda F, Baro T, Iglesias M, Virtanen I and Garcia DH: Snail1 protein in the stroma as a new putative prognosis marker for colon tumours. PLoS One. 4:e55952009.

54. 

Bieche I, Lerebours F, Tozlu S, Espie M, Marty M and Lidereau R: Molecular profiling of inflammatory breast cancer: identification of a poor-prognosis gene expression signature. Clin Cancer Res. 10:6789–6795. 2004.

55. 

Sarkar FH, Li Y, Wang Z and Kong D: Pancreatic cancer stem cells and EMT in drug resistance and metastasis. Minerva Chir. 64:489–500. 2009.

56. 

van Zijl F, Zulehner G, Petz M, et al: Epithelial-mesenchymal transition in hepatocellular carcinoma. Future Oncol. 5:1169–1179. 2009.

57. 

Sabbah M, Emami S, Redeuilh G, et al: Molecular signature and therapeutic perspective of the epithelial-to-mesenchymal transitions in epithelial cancers. Drug Resist Updat. 11:123–151. 2008.

58. 

Thiery JP, Chua K, Sim WJ and Huang R: Epithelial mesenchymal transition during development in fibrosis and in the progression of carcinoma. Bull Cancer. 97:1285–1295. 2010.(In French).

59. 

Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA and Lander ES: Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 138:645–659. 2009.

60. 

Ketola K, Hilvo M, Hyotylainen T, et al: Salinomycin inhibits prostate cancer growth and migration via induction of oxidative stress. Br J Cancer. 106:99–106. 2012.

61. 

Wang Y: Effects of salinomycin on cancer stem cell in human lung adenocarcinoma A549 cells. Med Chem. 7:106–111. 2011.

62. 

Gong C, Yao H, Liu Q, Chen J, Shi J, Su F and Song E: Markers of tumor-initiating cells predict chemoresistance in breast cancer. PLoS One. 5:e156302010.

63. 

Bardsley MR, Horvath VJ, Asuzu DT, et al: Kitlow stem cells cause resistance to Kit/platelet-derived growth factor alpha inhibitors in murine gastrointestinal stromal tumors. Gastroenterology. 139:942–952. 2010.

64. 

Fuchs D, Daniel V, Sadeghi M, Opelz G and Naujokat C: Salinomycin overcomes ABC transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like KG-1a cells. Biochem Biophys Res Commun. 394:1098–1104. 2010.

65. 

Jones PA and Taylor SM: Cellular differentiation, cytidine analogs and DNA methylation. Cell. 20:85–93. 1980.

66. 

Jones PA, Taylor SM and Wilson V: DNA modification, differentiation, and transformation. J Exp Zool. 228:287–295. 1983.

67. 

Fraga MF, Herranz M, Espada J, et al: A mouse skin multistage carcinogenesis model reflects the aberrant DNA methylation patterns of human tumors. Cancer Res. 64:5527–5534. 2004.

68. 

Herranz N, Pasini D, Diaz VM, et al: Polycomb complex 2 is required for E-cadherin repression by the Snail1 transcription factor. Mol Cell Biol. 28:4772–4781. 2008.

69. 

Vincent A and Van SI: On the epigenetic origin of cancer stem cells. Biochim Biophys Acta. 1826:83–88. 2012.

70. 

Rodriguez-Paredes M and Esteller M: Cancer epigenetics reaches mainstream oncology. Nat Med. 17:330–339. 2011.

71. 

Ehrlich M: DNA hypomethylation in cancer cells. Epigenomics. 1:239–259. 2009.

72. 

Ehrlich M: DNA methylation in cancer: too much, but also too little. Oncogene. 21:5400–5413. 2002.

73. 

Fullgrabe J, Kavanagh E and Joseph B: Histone onco-modifications. Oncogene. 30:3391–3403. 2011.

74. 

Maeda G, Chiba T, Aoba T and Imai K: Epigenetic inactivation of E-cadherin by promoter hypermethylation in oral carcinoma cells. Odontology. 95:24–29. 2007.

75. 

Lombaerts M, van Wezel T, Philippo K, et al: E-cadherin transcriptional downregulation by promoter methylation but not mutation is related to epithelial-to-mesenchymal transition in breast cancer cell lines. Br J Cancer. 94:661–671. 2006.

76. 

Savagner P: The epithelial-mesenchymal transition (EMT) phenomenon. Ann Oncol. 21(Suppl 7): vii89–vii92. 2010.

77. 

Lin T, Ponn A, Hu X, Law BK and Lu J: Requirement of the histone demethylase LSD1 in Snai1-mediated transcriptional repression during epithelial-mesenchymal transition. Oncogene. 29:4896–4904. 2010.

78. 

Yang F, Sun L, Li Q, Han X, Lei L, Zhang H and Shang Y: SET8 promotes epithelial-mesenchymal transition and confers TWIST dual transcriptional activities. EMBO J. 31:110–123. 2011.

79. 

Kalakonda N, Fischle W, Boccuni P, et al: Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1. Oncogene. 27:4293–4304. 2008.

80. 

Li Z, Nie F, Wang S and Li L: Histone H4 Lys 20 monomethylation by histone methylase SET8 mediates Wnt target gene activation. Proc Natl Acad Sci USA. 108:3116–3123. 2011.

81. 

Bernstein BE, Mikkelsen TS, Xie X, et al: A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell. 125:315–326. 2006.

82. 

Mongroo PS and Rustgi AK: The role of the miR-200 family in epithelial-mesenchymal transition. Cancer Biol Ther. 10:219–222. 2010.

83. 

Bullock MD, Sayan AE, Packham GK and Mirnezami AH: MicroRNAs: critical regulators of epithelial to mesenchymal (EMT) and mesenchymal to epithelial transition (MET) in cancer progression. Biol Cell. 104:3–12. 2012.

84. 

Vrba L, Jensen TJ, Garbe JC, et al: Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells. PLoS One. 5:e86972010.

85. 

Davalos V, Moutinho C, Villanueva A, Boque R, Silva P, Carneiro F and Esteller M: Dynamic epigenetic regulation of the microRNA-200 family mediates epithelial and mesenchymal transitions in human tumorigenesis. Oncogene. 31:2062–2074. 2012.

86. 

Wiklund ED, Bramsen JB, Hulf T, et al: Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer. Int J Cancer. 128:1327–1334. 2011.

87. 

Neves R, Scheel C, Weinhold S, et al: Role of DNA methylation in miR-200c/141 cluster silencing in invasive breast cancer cells. BMC Res Notes. 3:2192010.

88. 

Tryndyak VP, Beland FA and Pogribny IP: E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells. Int J Cancer. 126:2575–2583. 2010.

89. 

Kelly TK, De Carvalho DD and Jones PA: Epigenetic modifications as therapeutic targets. Nat Biotechnol. 28:1069–1078. 2010.

90. 

Lane AA and Chabner BA: Histone deacetylase inhibitors in cancer therapy. J Clin Oncol. 27:5459–5468. 2009.

91. 

Stintzing S, Kemmerling R, Kiesslich T, Alinger B, Ocker M and Neureiter D: Myelodysplastic syndrome and histone deacetylase inhibitors: “to be or not to be acetylated”? J Biomed Biotechnol. 2011:2141432011.

92. 

Batty N, Malouf GG and Issa JP: Histone deacetylase inhibitors as anti-neoplastic agents. Cancer Lett. 280:192–200. 2009.

93. 

Ocker M: Deacetylase inhibitors - focus on non-histone targets and effects. World J Biol Chem. 1:55–61. 2010.

94. 

Ocker M and Schneider-Stock R: Histone deacetylase inhibitors: signalling towards p21cip1/waf1. Int J Biochem Cell Biol. 39:1367–1374. 2007.

95. 

Spange S, Wagner T, Heinzel T and Kramer OH: Acetylation of non-histone proteins modulates cellular signalling at multiple levels. Int J Biochem Cell Biol. 41:185–198. 2009.

96. 

Di Fazio P, Schneider-Stock R, Neureiter D, et al: The pan-deacetylase inhibitor panobinostat inhibits growth of hepatocellular carcinoma models by alternative pathways of apoptosis. Cell Oncol. 32:285–300. 2010.

97. 

Di Fazio P, Montalbano R, Quint K, et al: The pan-deacetylase inhibitor panobinostat modulates expression of epithelialmesenchymal transition markers in hepatocellular carcinoma models. Oncol Lett. (In press).

98. 

Neureiter D, Zopf S, Leu T, et al: Apoptosis, proliferation and differentiation patterns are influenced by Zebularine and SAHA in pancreatic cancer models. Scand J Gastroenterol. 42:103–116. 2007.

99. 

Ryningen A, Stapnes C and Bruserud O: Clonogenic acute myelogenous leukemia cells are heterogeneous with regard to regulation of differentiation and effect of epigenetic pharmacological targeting. Leuk Res. 31:1303–1313. 2007.

100. 

Todaro M, Francipane MG, Medema JP and Stassi G: Colon cancer stem cells: promise of targeted therapy. Gastroenterology. 138:2151–2162. 2010.

101. 

Ivanova T, Zouridis H, Wu Y, et al: Integrated epigenomics identifies BMP4 as a modulator of cisplatin sensitivity in gastric cancer. Gut. Apr 25–2012.(E-pub ahead of print).

102. 

Bhatla T, Wang J, Morrison DJ, Raetz EA, Burke MJ, Brown P and Carroll WL: Epigenetic reprogramming reverses the relapse-specific gene expression signature and restores chemo-sensitivity in childhood B-lymphoblastic leukemia. Blood. 119:5201–5210. 2012.

103. 

Omenetti A, Bass LM, Anders RA, et al: Hedgehog activity, epithelial-mesenchymal transitions, and biliary dysmorphogenesis in biliary atresia. Hepatology. 53:1246–1258. 2011.

104. 

Fabris L and Strazzabosco M: Epithelial-mesenchymal interactions in biliary diseases. Semin Liver Dis. 31:11–32. 2011.

105. 

Bailey JM, Singh PK and Hollingsworth MA: Cancer metastasis facilitated by developmental pathways: Sonic hedgehog, Notch, and bone morphogenic proteins. J Cell Biochem. 102:829–839. 2007.

106. 

Dasgupta P, Rizwani W, Pillai S, et al: Nicotine induces cell proliferation, invasion and epithelial-mesenchymal transition in a variety of human cancer cell lines. Int J Cancer. 124:36–45. 2009.

107. 

Li Y, Liu Y, Xu Y, Voorhees JJ and Fisher GJ: UV irradiation induces Snail expression by AP-1 dependent mechanism in human skin keratinocytes. J Dermatol Sci. 60:105–113. 2010.

108. 

Hardy KM, Booth BW, Hendrix MJ, Salomon DS and Strizzi L: ErbB/EGF signaling and EMT in mammary development and breast cancer. J Mammary Gland Biol Neoplasia. 15:191–199. 2010.

109. 

Guttilla IK, Adams BD and White BA: ERalpha, microRNAs, and the epithelial-mesenchymal transition in breast cancer. Trends Endocrinol Metab. 23:73–82. 2012.

110. 

Gallo D, Ferlini C and Scambia G: The epithelial-mesenchymal transition and the estrogen-signaling in ovarian cancer. Curr Drug Targets. 11:474–481. 2010.

111. 

Katoh Y and Katoh M: FGFR2-related pathogenesis and FGFR2-targeted therapeutics (Review). Int J Mol Med. 23:307–311. 2009.

112. 

Ding W, You H, Dang H, et al: Epithelial-to-mesenchymal transition of murine liver tumor cells promotes invasion. Hepatology. 52:945–953. 2010.

113. 

Semenza GL: Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy. Trends Pharmacol Sci. 33:207–214. 2012.

114. 

Jiang J, Tang YL and Liang XH: EMT: a new vision of hypoxia promoting cancer progression. Cancer Biol Ther. 11:714–723. 2011.

115. 

Yang SY, Miah A, Pabari A and Winslet M: Growth Factors and their receptors in cancer metastases. Front Biosci. 16:531–538. 2011.

116. 

Mamuya FA and Duncan MK: aV integrins and TGF-β-induced EMT: a circle of regulation. J Cell Mol Med. 16:445–455. 2012.

117. 

Eble JA and Haier J: Integrins in cancer treatment. Curr Cancer Drug Targets. 6:89–105. 2006.

118. 

Lahsnig C, Mikula M, Petz M, et al: ILEI requires oncogenic Ras for the epithelial to mesenchymal transition of hepatocytes and liver carcinoma progression. Oncogene. 28:638–650. 2009.

119. 

Yadav A, Kumar B, Datta J, Teknos TN and Kumar P: IL-6 promotes head and neck tumor metastasis by inducing epithelialmesenchymal transition via the JAK-STAT3-SNAIL signaling pathway. Mol Cancer Res. 9:1658–1667. 2011.

120. 

Andrae J, Gallini R and Betsholtz C: Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 22:1276–1312. 2008.

121. 

Peebles KA, Lee JM, Mao JT, et al: Inflammation and lung carcinogenesis: applying findings in prevention and treatment. Expert Rev Anticancer Ther. 7:1405–1421. 2007.

122. 

Lee JM, Yanagawa J, Peebles KA, Sharma S, Mao JT and Dubinett SM: Inflammation in lung carcinogenesis: new targets for lung cancer chemoprevention and treatment. Crit Rev Oncol Hematol. 66:208–217. 2008.

123. 

Gherardi E, Birchmeier W, Birchmeier C and Vande WG: Targeting MET in cancer: rationale and progress. Nat Rev Cancer. 12:89–103. 2012.

124. 

Tolnay E, Kuhnen C, Wiethege T, Konig JE, Voss B and Muller KM: Hepatocyte growth factor/scatter factor and its receptor c-Met are overexpressed and associated with an increased microvessel density in malignant pleural mesothelioma. J Cancer Res Clin Oncol. 124:291–296. 1998.

125. 

Heuberger J and Birchmeier W: Interplay of cadherin-mediated cell adhesion and canonical Wnt signaling. Cold Spring Harb Perspect Biol. 2:a0029152010.

126. 

Hollier BG, Evans K and Mani SA: The epithelial-to-mesenchymal transition and cancer stem cells: a coalition against cancer therapies. J Mammary Gland Biol Neoplasia. 14:29–43. 2009.

127. 

Mimeault M and Batra SK: New advances on critical implications of tumor- and metastasis-initiating cells in cancer progression, treatment resistance and disease recurrence. Histol Histopathol. 25:1057–1073. 2010.

128. 

Singh A and Settleman J: EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene. 29:4741–4751. 2010.

129. 

Wang Z, Li Y, Ahmad A, Azmi AS, Kong D, Banerjee S and Sarkar FH: Targeting miRNAs involved in cancer stem cell and EMT regulation: an emerging concept in overcoming drug resistance. Drug Resist Updat. 13:109–118. 2010.

130. 

Wellner U, Schubert J, Burk UC, et al: The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol. 11:1487–1495. 2009.

131. 

Wendt MK, Tian M and Schiemann WP: Deconstructing the mechanisms and consequences of TGF-beta-induced EMT during cancer progression. Cell Tissue Res. 347:85–101. 2012.

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kiesslich T, Pichler M and Neureiter D: Epigenetic control of epithelial-mesenchymal-transition in human cancer (Review). Mol Clin Oncol 1: 3-11, 2013.
APA
Kiesslich, T., Pichler, M., & Neureiter, D. (2013). Epigenetic control of epithelial-mesenchymal-transition in human cancer (Review). Molecular and Clinical Oncology, 1, 3-11. https://doi.org/10.3892/mco.2012.28
MLA
Kiesslich, T., Pichler, M., Neureiter, D."Epigenetic control of epithelial-mesenchymal-transition in human cancer (Review)". Molecular and Clinical Oncology 1.1 (2013): 3-11.
Chicago
Kiesslich, T., Pichler, M., Neureiter, D."Epigenetic control of epithelial-mesenchymal-transition in human cancer (Review)". Molecular and Clinical Oncology 1, no. 1 (2013): 3-11. https://doi.org/10.3892/mco.2012.28
Copy and paste a formatted citation
x
Spandidos Publications style
Kiesslich T, Pichler M and Neureiter D: Epigenetic control of epithelial-mesenchymal-transition in human cancer (Review). Mol Clin Oncol 1: 3-11, 2013.
APA
Kiesslich, T., Pichler, M., & Neureiter, D. (2013). Epigenetic control of epithelial-mesenchymal-transition in human cancer (Review). Molecular and Clinical Oncology, 1, 3-11. https://doi.org/10.3892/mco.2012.28
MLA
Kiesslich, T., Pichler, M., Neureiter, D."Epigenetic control of epithelial-mesenchymal-transition in human cancer (Review)". Molecular and Clinical Oncology 1.1 (2013): 3-11.
Chicago
Kiesslich, T., Pichler, M., Neureiter, D."Epigenetic control of epithelial-mesenchymal-transition in human cancer (Review)". Molecular and Clinical Oncology 1, no. 1 (2013): 3-11. https://doi.org/10.3892/mco.2012.28
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team