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PMID: 20646772 Published · ppublish English Journal Article Research Support, N.I.H., Intramural Review

Epigenetic regulation of cancer stem cells in liver cancer: current concepts and clinical implications.

Journal of hepatology ·Vol. 53 ·No. 3 ·2010-09-00 ·Pages 568-77

Marquardt JU, Factor VM, Thorgeirsson SS

Abstract

The two dominant models of carcinogenesis postulate stochastic (clonal evolution) or hierarchic organization of tumor (cancer stem cell model). According to the latter, at the germinal center of tumor evolution is a cancer stem cell (CSC) which, similar to normal adult stem cells, possesses the capacity of self-renewal and a differentiation potential. Over the past few years, compelling evidence has emerged in support of the hierarchic cancer model for many solid tumors including hepatocellular cancers. The CSCs are posited to be responsible not only for tumor initiation but also for the generation of distant metastasis and relapse after therapy. These characteristics are particularly relevant for a multi-resistant tumor entity like human hepatocellular carcinoma and may herald a paradigm shift in the management of this deadly disease. Identification and detailed characterization of liver CSCs is therefore imperative for improving prevention approaches, enhancing early detection, and extending the limited treatment options. Despite the current progress in understanding the contribution of CSCs to the generation of heterogeneity of tumors, the molecular complexity and exact regulation of CSCs is poorly understood. This review focuses on the genetic and epigenetic mechanisms that regulate and define the unique CSC properties with an emphasis on key regulatory pathways of liver CSCs and their clinical significance.

MeSH Terms
AC133 Antigen Aldehyde Dehydrogenase/metabolism Antigens, CD/metabolism Antigens, Neoplasm/metabolism Carcinoma, Hepatocellular/genetics,metabolism,pathology,secondary Cell Adhesion Molecules/metabolism Cell Division Cell Separation/methods Epigenesis, Genetic Epithelial Cell Adhesion Molecule Genes, myc Glycoproteins/metabolism Hedgehog Proteins/metabolism Humans Liver Neoplasms/genetics,metabolism,pathology MicroRNAs/genetics Models, Biological Neoplasm Metastasis/genetics,pathology Neoplastic Stem Cells/pathology,physiology Nuclear Proteins/genetics Peptides/metabolism Polycomb Repressive Complex 1 Proto-Oncogene Proteins/genetics RNA, Neoplasm/genetics Receptors, Notch/metabolism Repressor Proteins/genetics Signal Transduction Thy-1 Antigens/metabolism Transforming Growth Factor beta/metabolism Wnt Proteins/metabolism beta Catenin/metabolism
Chemicals
AC133 Antigen Antigens, CD Antigens, Neoplasm BMI1 protein, human CTNNB1 protein, human Cell Adhesion Molecules EPCAM protein, human Epithelial Cell Adhesion Molecule Glycoproteins Hedgehog Proteins MicroRNAs Nuclear Proteins Peptides Proto-Oncogene Proteins RNA, Neoplasm Receptors, Notch Repressor Proteins SHH protein, human Thy-1 Antigens Transforming Growth Factor beta Wnt Proteins beta Catenin Aldehyde Dehydrogenase Polycomb Repressive Complex 1
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Marquardt J U
Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, MD, USA.
Factor V M
Thorgeirsson S S
References (160)
160 references, click to expand
  1. Cancer stem cells: cell culture, markers, and targets for new therapies.
    J Cell Biochem. 2009 Dec 1;108(5):1031-8 PMID: 19760641
  2. A module map showing conditional activity of expression modules in cancer.
    Nat Genet. 2004 Oct;36(10):1090-8 PMID: 15448693
  3. Sorafenib in advanced hepatocellular carcinoma.
    N Engl J Med. 2008 Jul 24;359(4):378-90 PMID: 18650514
  4. MicroRNA expression, survival, and response to interferon in liver cancer.
    N Engl J Med. 2009 Oct 8;361(15):1437-47 PMID: 19812400
  5. Stem cells and cancer; the polycomb connection.
    Cell. 2004 Aug 20;118(4):409-18 PMID: 15315754
  6. Breast tumor heterogeneity: cancer stem cells or clonal evolution?
    Cell Cycle. 2007 Oct 1;6(19):2332-8 PMID: 17786053
  7. Anti-CD38 antibody-mediated clearance of human repopulating cells masks the heterogeneity of leukemia-initiating cells.
    Blood. 2008 Aug 1;112(3):568-75 PMID: 18523148
  8. Identifying cancer stem cells in solid tumors: case not proven.
    Cancer Res. 2006 Feb 15;66(4):1891-5; discussion 1890 PMID: 16488984
  9. Promoter hypomethylation regulates CD133 expression in human gliomas.
    Cell Res. 2008 Oct;18(10):1037-46 PMID: 18679414
  10. WNT and beta-catenin signalling: diseases and therapies.
    Nat Rev Genet. 2004 Sep;5(9):691-701 PMID: 15372092
  11. Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling.
    Hepatology. 2004 Sep;40(3):667-76 PMID: 15349906
  12. Primary bioassay of human tumor stem cells.
    Science. 1977 Jul 29;197(4302):461-3 PMID: 560061
  13. Application of comparative functional genomics to identify best-fit mouse models to study human cancer.
    Nat Genet. 2004 Dec;36(12):1306-11 PMID: 15565109
  14. Sphere-forming stem-like cell populations with drug resistance in human sarcoma cell lines.
    Int J Oncol. 2009 May;34(5):1381-6 PMID: 19360350
  15. Aberrant CpG island hypermethylation along multistep hepatocarcinogenesis.
    Am J Pathol. 2003 Oct;163(4):1371-8 PMID: 14507645
  16. Octamer 4 small interfering RNA results in cancer stem cell-like cell apoptosis.
    Cancer Res. 2008 Aug 15;68(16):6533-40 PMID: 18701476
  17. Identification of local and circulating cancer stem cells in human liver cancer.
    Hepatology. 2008 Mar;47(3):919-28 PMID: 18275073
  18. Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells.
    Hepatology. 2009 Aug;50(2):472-80 PMID: 19585654
  19. Cancer stem cells.
    N Engl J Med. 2006 Sep 21;355(12):1253-61 PMID: 16990388
  20. Role of the murine reprogramming factors in the induction of pluripotency.
    Cell. 2009 Jan 23;136(2):364-77 PMID: 19167336
  21. Liver stem cells and hepatocellular carcinoma.
    Hepatology. 2009 Jan;49(1):318-29 PMID: 19111019
  22. DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction.
    Nat Genet. 2009 Nov;41(11):1207-15 PMID: 19801979
  23. MicroRNAs and cancer: short RNAs go a long way.
    Cell. 2009 Feb 20;136(4):586-91 PMID: 19239879
  24. Notch signalling in cancer stem cells.
    Clin Transl Oncol. 2009 Jan;11(1):11-9 PMID: 19155199
  25. Stem cells in hepatocarcinogenesis: evidence from genomic data.
    Semin Liver Dis. 2010 Feb;30(1):26-34 PMID: 20175031
  26. Post-transcriptional down-regulation of Atoh1/Math1 by bone morphogenic proteins suppresses medulloblastoma development.
    Genes Dev. 2008 Mar 15;22(6):722-7 PMID: 18347090
  27. Wnt/beta-catenin signaling regulates cancer stem cells in lung cancer A549 cells.
    Biochem Biophys Res Commun. 2010 Feb 12;392(3):373-9 PMID: 20074550
  28. Tumor heterogeneity.
    Cancer Res. 1984 Jun;44(6):2259-65 PMID: 6372991
  29. Functional evidence that the self-renewal gene NANOG regulates human tumor development.
    Stem Cells. 2009 May;27(5):993-1005 PMID: 19415763
  30. Modelling Myc inhibition as a cancer therapy.
    Nature. 2008 Oct 2;455(7213):679-83 PMID: 18716624
  31. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.
    Cell. 2006 Aug 25;126(4):663-76 PMID: 16904174
  32. CD133 is a marker of bioenergetic stress in human glioma.
    PLoS One. 2008;3(11):e3655 PMID: 18985161
  33. Chemotherapy-resistant side-population of colon cancer cells has a higher sensitivity to TRAIL than the non-SP, a higher expression of c-Myc and TRAIL-receptor DR4.
    Cancer Biol Ther. 2007 Sep;6(9):1490-5 PMID: 17881904
  34. Growth characteristics of a mouse plasma cell tumor.
    Cancer Res. 1968 Nov;28(11):2187-96 PMID: 5723963
  35. A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells.
    Nat Med. 2006 Apr;12(4):410-6 PMID: 16532004
  36. Resection and liver transplantation for hepatocellular carcinoma.
    Semin Liver Dis. 2005;25(2):181-200 PMID: 15918147
  37. Tumour stem cells and drug resistance.
    Nat Rev Cancer. 2005 Apr;5(4):275-84 PMID: 15803154
  38. Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning.
    Nat Med. 2003 Apr;9(4):416-23 PMID: 12640447
  39. Apoptosis: biochemical aspects and clinical implications.
    Clin Chim Acta. 2002 Dec;326(1-2):27-45 PMID: 12417095
  40. Identification of selective inhibitors of cancer stem cells by high-throughput screening.
    Cell. 2009 Aug 21;138(4):645-659 PMID: 19682730
  41. EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features.
    Gastroenterology. 2009 Mar;136(3):1012-24 PMID: 19150350
  42. Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets.
    Hepatology. 2007 Jan;45(1):42-52 PMID: 17187432
  43. Role of Sox-9, ER81 and VE-cadherin in retinoic acid-mediated trans-differentiation of breast cancer cells.
    PLoS One. 2008 Jul 16;3(7):e2714 PMID: 18628953
  44. Stem cells and liver regeneration.
    Gastroenterology. 2009 Aug;137(2):466-81 PMID: 19470389
  45. Pluripotency redux--advances in stem-cell research.
    N Engl J Med. 2007 Oct 11;357(15):1469-72 PMID: 17928593
  46. Prospective identification of tumorigenic breast cancer cells.
    Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8 PMID: 12629218
  47. Notch signaling controls liver development by regulating biliary differentiation.
    Development. 2009 May;136(10):1727-39 PMID: 19369401
  48. The history of cancer epigenetics.
    Nat Rev Cancer. 2004 Feb;4(2):143-53 PMID: 14732866
  49. miR-221 overexpression contributes to liver tumorigenesis.
    Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):264-9 PMID: 20018759
  50. Embryonic stem cell markers expression in cancers.
    Biochem Biophys Res Commun. 2009 May 29;383(2):157-62 PMID: 19268426
  51. The overexpression of polycomb group proteins Bmi1 and EZH2 is associated with the progression and aggressive biological behavior of hepatocellular carcinoma.
    Lab Invest. 2008 Aug;88(8):873-82 PMID: 18591938
  52. Expansion of liver cancer stem cells during aging in methionine adenosyltransferase 1A-deficient mice.
    Hepatology. 2008 Apr;47(4):1288-97 PMID: 18167064
  53. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores.
    Nat Genet. 2009 Feb;41(2):178-186 PMID: 19151715
  54. Transforming growth factor-beta signaling in stem cells and cancer.
    Science. 2005 Oct 7;310(5745):68-71 PMID: 16210527
  55. MicroRNAs and parallel stem cell lives.
    Cell. 2009 Aug 7;138(3):423-4 PMID: 19665962
  56. Liver stem cells: implications for hepatocarcinogenesis.
    Stem Cell Rev. 2005;1(3):253-60 PMID: 17142862
  57. Hepatocellular carcinoma pathogenesis: from genes to environment.
    Nat Rev Cancer. 2006 Sep;6(9):674-87 PMID: 16929323
  58. Comparative and integrative functional genomics of HCC.
    Oncogene. 2006 Jun 26;25(27):3801-9 PMID: 16799621
  59. Identification and expansion of human colon-cancer-initiating cells.
    Nature. 2007 Jan 4;445(7123):111-5 PMID: 17122771
  60. Isolation of circulating epithelial and tumor progenitor cells with an invasive phenotype from breast cancer patients.
    Int J Cancer. 2010 Feb 1;126(3):669-83 PMID: 19662651
  61. The STAT3 inhibitor NSC 74859 is effective in hepatocellular cancers with disrupted TGF-beta signaling.
    Oncogene. 2009 Feb 19;28(7):961-72 PMID: 19137011
  62. Studies of the dissemination and quantitative transplantation of a lymphocytic leukaemia of CBA mice.
    Br J Cancer. 1958 Sep;12(3):378-401 PMID: 13596492
  63. Distinct thresholds govern Myc's biological output in vivo.
    Cancer Cell. 2008 Dec 9;14(6):447-57 PMID: 19061836
  64. Genetic programming of liver and pancreas progenitors: lessons for stem-cell differentiation.
    Nat Rev Genet. 2008 May;9(5):329-40 PMID: 18398419
  65. Suppression of tumorigenesis and activation of Wnt signaling by bone morphogenetic protein 4 in human cancer cells.
    Cancer Biol Ther. 2004 Jul;3(7):667-75 PMID: 15197354
  66. Identification and characterization of tumorigenic liver cancer stem/progenitor cells.
    Gastroenterology. 2007 Jun;132(7):2542-56 PMID: 17570225
  67. Oligonucleotide microarray for prediction of early intrahepatic recurrence of hepatocellular carcinoma after curative resection.
    Lancet. 2003 Mar 15;361(9361):923-9 PMID: 12648972
  68. Mathematical model for chemotherapeutic drug efficacy in arresting tumour growth based on the cancer stem cell hypothesis.
    Cell Prolif. 2007 Jun;40(3):338-54 PMID: 17531079
  69. Molecular targeted therapies in hepatocellular carcinoma.
    Hepatology. 2008 Oct;48(4):1312-27 PMID: 18821591
  70. Tumor self-seeding by circulating cancer cells.
    Cell. 2009 Dec 24;139(7):1315-26 PMID: 20064377
  71. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell.
    Nat Med. 1997 Jul;3(7):730-7 PMID: 9212098
  72. Central role of c-Myc during malignant conversion in human hepatocarcinogenesis.
    Cancer Res. 2009 Apr 1;69(7):2775-82 PMID: 19276364
  73. Mechanistic and prognostic significance of aberrant methylation in the molecular pathogenesis of human hepatocellular carcinoma.
    J Clin Invest. 2007 Sep;117(9):2713-22 PMID: 17717605
  74. Tumor growth need not be driven by rare cancer stem cells.
    Science. 2007 Jul 20;317(5836):337 PMID: 17641192
  75. Progenitor cells in liver regeneration: molecular responses controlling their activation and expansion.
    APMIS. 2005 Nov-Dec;113(11-12):876-902 PMID: 16480456
  76. Wnt/beta-catenin signaling contributes to activation of normal and tumorigenic liver progenitor cells.
    Cancer Res. 2008 Jun 1;68(11):4287-95 PMID: 18519688
  77. CD133 is indicative for a resistance phenotype but does not represent a prognostic marker for survival of non-small cell lung cancer patients.
    Int J Cancer. 2010 Feb 15;126(4):950-8 PMID: 19676044
  78. Regulating cancer stem cells the miR way.
    Cell Stem Cell. 2010 Jan 8;6(1):4-6 PMID: 20085735
  79. Monoclonal antibody CD133-2 (AC141) against hematopoietic stem cell antigen CD133 shows crossreactivity with cytokeratin 18.
    J Histochem Cytochem. 2002 Aug;50(8):1131-4 PMID: 12133915
  80. Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells.
    Biochem Biophys Res Commun. 2006 Dec 29;351(4):820-4 PMID: 17097610
  81. Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma.
    Cancer Res. 2009 Sep 15;69(18):7385-92 PMID: 19723656
  82. Hedgehog signaling in hepatocellular carcinoma: novel therapeutic strategy targeting hedgehog signaling in HCC.
    Cancer Biol Ther. 2006 Feb;5(2):238-9 PMID: 16552173
  83. Tumour CD133 mRNA expression and clinical outcome in surgically resected colorectal cancer patients.
    Eur J Cancer. 2010 Feb;46(3):642-9 PMID: 20005089
  84. Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells.
    Cell. 2009 Aug 7;138(3):592-603 PMID: 19665978
  85. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo.
    J Exp Med. 1996 Apr 1;183(4):1797-806 PMID: 8666936
  86. Module map of stem cell genes guides creation of epithelial cancer stem cells.
    Cell Stem Cell. 2008 Apr 10;2(4):333-44 PMID: 18397753
  87. Redefining the target again: chemotherapeutics as vascular disrupting agents?
    Cancer Cell. 2008 Sep 9;14(3):195-6 PMID: 18772108
  88. c-Myc is required for maintenance of glioma cancer stem cells.
    PLoS One. 2008;3(11):e3769 PMID: 19020659
  89. Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens.
    Cell Stem Cell. 2009 Jun 5;4(6):568-80 PMID: 19497285
  90. Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas.
    Nature. 2004 Mar 18;428(6980):337-41 PMID: 15029199
  91. Context, tissue plasticity, and cancer: are tumor stem cells also regulated by the microenvironment?
    Cancer Cell. 2005 Jan;7(1):17-23 PMID: 15652746
  92. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions.
    Nat Rev Cancer. 2008 Oct;8(10):755-68 PMID: 18784658
  93. Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content.
    Cell. 2010 Jan 8;140(1):62-73 PMID: 20074520
  94. Microenvironmental modulation of asymmetric cell division in human lung cancer cells.
    Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2195-200 PMID: 20080668
  95. Glioma stem cells: better flat than round.
    Cell Stem Cell. 2009 Jun 5;4(6):466-7 PMID: 19497271
  96. Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy.
    J Clin Oncol. 2008 Jun 10;26(17):2813-20 PMID: 18539959
  97. Recurrence of hepatocellular carcinoma following liver transplantation: a review of preoperative and postoperative prognostic indicators.
    Arch Surg. 2008 Feb;143(2):182-8; discussion 188 PMID: 18283144
  98. Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature.
    Cancer Res. 2009 Feb 15;69(4):1302-13 PMID: 19190339
  99. The polycomb gene product BMI1 contributes to the maintenance of tumor-initiating side population cells in hepatocellular carcinoma.
    Cancer Res. 2008 Oct 1;68(19):7742-9 PMID: 18829528
  100. MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer.
    Nature. 2004 Oct 28;431(7012):1112-7 PMID: 15475948
  101. The epigenetic progenitor origin of human cancer.
    Nat Rev Genet. 2006 Jan;7(1):21-33 PMID: 16369569
  102. Characterization of a side population of cancer cells from human gastrointestinal system.
    Stem Cells. 2006 Mar;24(3):506-13 PMID: 16239320
  103. The Wnt-dependent signaling pathways as target in oncology drug discovery.
    Invest New Drugs. 2006 Jul;24(4):263-80 PMID: 16683072
  104. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells.
    Nature. 2003 May 15;423(6937):302-5 PMID: 12714971
  105. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer.
    Cell Stem Cell. 2007 Sep 13;1(3):313-23 PMID: 18371365
  106. Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties.
    Hepatology. 2006 Jul;44(1):240-51 PMID: 16799977
  107. The clonal evolution of tumor cell populations.
    Science. 1976 Oct 1;194(4260):23-8 PMID: 959840
  108. Metastasis: from dissemination to organ-specific colonization.
    Nat Rev Cancer. 2009 Apr;9(4):274-84 PMID: 19308067
  109. Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients.
    Breast Cancer Res. 2009;11(4):R46 PMID: 19589136
  110. Depletion of embryonic stem cell signature by histone deacetylase inhibitor in NCCIT cells: involvement of Nanog suppression.
    Cancer Res. 2009 Jul 15;69(14):5716-25 PMID: 19567677
  111. MiR-222 overexpression confers cell migratory advantages in hepatocellular carcinoma through enhancing AKT signaling.
    Clin Cancer Res. 2010 Feb 1;16(3):867-75 PMID: 20103675
  112. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line.
    Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):781-6 PMID: 14711994
  113. Gene expression in fixed tissues and outcome in hepatocellular carcinoma.
    N Engl J Med. 2008 Nov 6;359(19):1995-2004 PMID: 18923165
  114. The bone marrow microenvironment as a tumor sanctuary and contributor to drug resistance.
    Clin Cancer Res. 2008 May 1;14(9):2519-26 PMID: 18451212
  115. Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells.
    Cancer Res. 2006 Oct 1;66(19):9339-44 PMID: 16990346
  116. Expansion of CD133-expressing liver cancer stem cells in liver-specific phosphatase and tensin homolog deleted on chromosome 10-deleted mice.
    Stem Cells. 2009 Feb;27(2):290-9 PMID: 19008348
  117. Genomics and signaling pathways in hepatocellular carcinoma.
    Semin Liver Dis. 2007 Feb;27(1):55-76 PMID: 17295177
  118. The emerging role of EpCAM in cancer and stem cell signaling.
    Cancer Res. 2009 Jul 15;69(14):5627-9 PMID: 19584271
  119. Epigenetic stem cell signature in cancer.
    Nat Genet. 2007 Feb;39(2):157-8 PMID: 17200673
  120. Stem cells, cancer, and cancer stem cells.
    Nature. 2001 Nov 1;414(6859):105-11 PMID: 11689955
  121. Activation of the hedgehog-signaling pathway in human cancer and the clinical implications.
    Oncogene. 2010 Jan 28;29(4):469-81 PMID: 19935712
  122. Clonogenic and nonclonogenic in vitro chemosensitivity assays.
    Cancer Treat Rep. 1985 Jun;69(6):615-32 PMID: 3893692
  123. Making a tumour's bed: glioblastoma stem cells and the vascular niche.
    Nat Rev Cancer. 2007 Oct;7(10):733-6 PMID: 17882276
  124. Resistance to cancer chemotherapy.
    Med Hypotheses. 1986 Feb;19(2):103-12 PMID: 3634906
  125. Notch signaling in development and cancer.
    Endocr Rev. 2007 May;28(3):339-63 PMID: 17409286
  126. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors.
    Nat Genet. 2008 May;40(5):499-507 PMID: 18443585
  127. Progenitor/stem cells give rise to liver cancer due to aberrant TGF-beta and IL-6 signaling.
    Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2445-50 PMID: 18263735
  128. Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells.
    Oncogene. 2009 Jan 15;28(2):209-18 PMID: 18836486
  129. Enhanced self-renewal capability in hepatic stem/progenitor cells drives cancer initiation.
    Gastroenterology. 2007 Sep;133(3):937-50 PMID: 17673212
  130. MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin1.
    Gastroenterology. 2008 Jul;135(1):257-69 PMID: 18555017
  131. Heterogeneity in cancer: cancer stem cells versus clonal evolution.
    Cell. 2009 Sep 4;138(5):822-9 PMID: 19737509
  132. Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties.
    Oncogene. 2009 Oct 8;28(40):3526-36 PMID: 19617899
  133. Genetic profiling of human hepatocellular carcinoma.
    Semin Liver Dis. 2005;25(2):125-32 PMID: 15918141
  134. Wnt signalling and cancer stem cells.
    Clin Transl Oncol. 2009 Jul;11(7):411-27 PMID: 19574199
  135. Transforming growth factor-beta gene expression signature in mouse hepatocytes predicts clinical outcome in human cancer.
    Hepatology. 2008 Jun;47(6):2059-67 PMID: 18506891
  136. Phenotypic plasticity and the epigenetics of human disease.
    Nature. 2007 May 24;447(7143):433-40 PMID: 17522677
  137. Cancer stem cell marker expression in hepatocellular carcinoma and liver metastases is not sufficient as single prognostic parameter.
    Cancer Lett. 2009 Mar 18;275(2):185-93 PMID: 19026485
  138. Cancer stem cell-directed therapies: recent data from the laboratory and clinic.
    Mol Ther. 2009 Feb;17(2):219-30 PMID: 19066601
  139. CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors.
    J Clin Invest. 2008 Jun;118(6):2111-20 PMID: 18497886
  140. Mining the Wnt pathway for cancer therapeutics.
    Nat Rev Drug Discov. 2006 Dec;5(12):997-1014 PMID: 17139285
  141. EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma.
    Cancer Res. 2008 Mar 1;68(5):1451-61 PMID: 18316609
  142. The prognostic role of a gene signature from tumorigenic breast-cancer cells.
    N Engl J Med. 2007 Jan 18;356(3):217-26 PMID: 17229949
  143. Circulating endothelial progenitor cells (EPC) for tumor vasculogenesis in gastric cancer patients.
    Cancer Lett. 2010 Feb 1;288(1):124-32 PMID: 19619937
  144. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits.
    Nat Rev Cancer. 2009 Apr;9(4):265-73 PMID: 19262571
  145. CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway.
    Oncogene. 2008 Mar 13;27(12):1749-58 PMID: 17891174
  146. Liver stem cells and tgf-Beta in hepatic carcinogenesis.
    Gastrointest Cancer Res. 2008 Jul;2(4 Suppl):S27-30 PMID: 19343145
  147. Deregulated expression of Notch receptors in human hepatocellular carcinoma.
    Dig Liver Dis. 2008 Feb;40(2):114-21 PMID: 17920003
  148. The expression pattern of PDX-1, SHH, Patched and Gli-1 is associated with pathological and clinical features in human pancreatic cancer.
    Pancreatology. 2009;9(1-2):116-26 PMID: 19077462
  149. "Stemness" genomics law governs clinical behavior of human cancer: implications for decision making in disease management.
    J Clin Oncol. 2008 Jun 10;26(17):2846-53 PMID: 18539963
  150. Identification of pancreatic cancer stem cells.
    Cancer Res. 2007 Feb 1;67(3):1030-7 PMID: 17283135
  151. The utility and limitations of glycosylated human CD133 epitopes in defining cancer stem cells.
    J Mol Med (Berl). 2008 Sep;86(9):1025-32 PMID: 18535813
  152. NOTCH signaling as a novel cancer therapeutic target.
    Curr Cancer Drug Targets. 2006 Jun;6(4):313-23 PMID: 16848722
  153. CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis.
    Cell. 2009 Jul 23;138(2):271-85 PMID: 19632178
  154. Identification of side population cells in human hepatocellular carcinoma cell lines with stepwise metastatic potentials.
    J Cancer Res Clin Oncol. 2008 Nov;134(11):1155-63 PMID: 18470535
  155. Normal stem cells and cancer stem cells: the niche matters.
    Cancer Res. 2006 May 1;66(9):4553-7 PMID: 16651403
  156. Differentiation therapy of hepatocellular carcinoma in mice with recombinant adenovirus carrying hepatocyte nuclear factor-4alpha gene.
    Hepatology. 2008 Nov;48(5):1528-39 PMID: 18925631
  157. Hepatocellular carcinoma.
    Lancet. 2003 Dec 6;362(9399):1907-17 PMID: 14667750
  158. MicroRNA regulation of cancer stem cells and therapeutic implications.
    AAPS J. 2009 Dec;11(4):682-92 PMID: 19842044
  159. Significance of CD90+ cancer stem cells in human liver cancer.
    Cancer Cell. 2008 Feb;13(2):153-66 PMID: 18242515
  160. Aldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populations.
    Mol Cancer Res. 2008 Jul;6(7):1146-53 PMID: 18644979
Article Info
Journal
Journal of hepatology
Abbr.
J Hepatol
ISSN
1600-0641
DOI
10.1016/j.jhep.2010.05.003
Published
2010-09-00
Epub
2010-00-31
Pages
568-77
Language
English
Region
Netherlands
NLM ID
8503886
PMCID
PMC3492877
Subset
IM
Grants
Intramural NIH HHS · ZIA BC011031-02 · United States
External Links
PubMed source DOI: 10.1016/j.jhep.2010.05.003 PMC Full Text View journal details
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