Cellular reprogramming and hepatocellular carcinoma development

World Journal of Gastroenterology

Volumn 19, Issue 47, 2013, Pages 8850-8860

  Zheng, Yun Wen ^a   Nie, Yun Zhong ^a,b   Taniguchi, Hideki ^a,c  

^a YOKOHAMA CITY UNIVERSITY   (Japan)

^b AFFILIATED HOSPITAL OF JIANGSU UNIVERSITY   (China)

^c YOKOHAMA CITY UNIVERSITY   (Japan)

Author keywords

Cancer stem cells; Hepatocellular carcinomas; Reprogramming; Therapeutics; Transcription factor

Indexed keywords

DOXORUBICIN; FLUOROURACIL; HYPOXIA INDUCIBLE FACTOR; IMATINIB; INTERLEUKIN 6; KRUPPEL LIKE FACTOR 4; MICRORNA; MICRORNA 148; MICRORNA 181; MICRORNA 302; MICROSOMAL AMINOPEPTIDASE; MITOGEN ACTIVATED PROTEIN KINASE; OCTAMER TRANSCRIPTION FACTOR 4; SOMATOMEDIN; SOMATOMEDIN RECEPTOR; SORAFENIB; TRANSCRIPTION FACTOR NANOG; TRANSCRIPTION FACTOR SOX2; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG;

ARTICLE; CANCER STEM CELL; CELL DIFFERENTIATION; DNA METHYLATION; GENE SILENCING; HUMAN; HYPOXIA; LIVER CELL CARCINOMA; NONHUMAN; NUCLEAR REPROGRAMMING; ONCOGENE C MYC; PROTEIN EXPRESSION; UPREGULATION; WNT SIGNALING PATHWAY;

CANCER STEM CELLS; HEPATOCELLULAR CARCINOMAS; REPROGRAMMING; THERAPEUTICS; TRANSCRIPTION FACTOR;

ANIMALS; CARCINOMA, HEPATOCELLULAR; CELL TRANSFORMATION, NEOPLASTIC; GENE EXPRESSION REGULATION, NEOPLASTIC; GENETIC THERAPY; HUMANS; LIVER NEOPLASMS; NEOPLASTIC STEM CELLS; NUCLEAR REPROGRAMMING; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS;

EID: 84890905450     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v19.i47.8850     Document Type: Article

References (116)

1. Ferlay J SH, Bray F, Forman D, Mathers C, Parkin DM. GLOBOCAN 2008 v2.0, Cancer incidence and mortality worldwide: IARC Cancer Base No. 10 (Internet). Lyon: International Agency for Research on Cancer, 2010. Available from: URL: http://globocan.iarc.fr Accessed on 28/8/2013
2. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61: 69-90[PMID: 21296855 DOI: 10.3322/caac.20107]
3. Yamamoto J, Kosuge T, Takayama T, Shimada K, Yama-saki S, Ozaki H, Yamaguchi N, Makuuchi M. Recurrence of hepatocellular carcinoma after surgery. Br J Surg 1996; 83: 1219-1222[PMID: 8983610 DOI: 10.1002/bjs.1800830913]
4. Nakai S, Masaki T, Shiratori Y, Ohgi T, Morishita A, Kuro-kohchi K, Watanabe S, Kuriyama S. Expression of p57(KIP2) in hepatocellular carcinoma: relationship between tumor differentiation and patient survival. Int J Oncol 2002; 20: 769-775[PMID: 11894123]
5. Schöniger-Hekele M, Hänel S, Wrba F, Müller C. Hepato-cellular carcinoma--survival and clinical characteristics in relation to various histologic molecular markers in Western patients. Liver Int 2005; 25: 62-69[PMID: 15698400 DOI: 10.1111/j.1478-3231.2004.0997.x]
6. EDMONDSON HA, STEINER PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer 1954; 7: 462-503[PMID: 13160935]
7. Zavaglia C, De Carlis L, Alberti AB, Minola E, Belli LS, Slim AO, Airoldi A, Giacomoni A, Rondinara G, Tinelli C, Forti D, Pinzello G. Predictors of long-term survival after liver transplantation for hepatocellular carcinoma. Am J Gastro-enterol 2005; 100: 2708-2716[PMID: 16393224 DOI: 10.1111/ j.1572-0241.2005.00289.x]
8. Hu TH, Huang CC, Lin PR, Chang HW, Ger LP, Lin YW, Changchien CS, Lee CM, Tai MH. Expression and prognostic role of tumor suppressor gene PTEN/MMAC1/TEP1 in hepatocellular carcinoma. Cancer 2003; 97: 1929-1940[PMID: 12673720 DOI: 10.1002/cncr.11266]
9. King KL, Li AF, Chau GY, Chi CW, Wu CW, Huang CL, Lui WY. Prognostic signifcance of heat shock protein-27 expression in hepatocellular carcinoma and its relation to histologic grading and survival. Cancer 2000; 88: 2464-2470[PMID: 10861421 DOI: 10.1002/1097-0142(20000601)88:11<2464:: AID-CNCR6>3.0.CO;2-W]
10. Endo K, Ueda T, Ueyama J, Ohta T, Terada T. Immunoreac-tive E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin proteins in hepatocellular carcinoma: relationships with tumor grade, clinicopathologic parameters, and patients' survival. Hum Pathol 2000; 31: 558-565[PMID: 10836294]
11. Villanueva A, Chiang DY, Newell P, Peix J, Thung S, Alsinet C, Tovar V, Roayaie S, Minguez B, Sole M, Battiston C, Van Laarhoven S, Fiel MI, Di Feo A, Hoshida Y, Yea S, Toffanin S, Ramos A, Martignetti JA, Mazzaferro V, Bruix J, Waxman S, Schwartz M, Meyerson M, Friedman SL, Llovet JM. Pivotal role of mTOR signaling in hepatocellular carcinoma. Gastro-enterology 2008; 135: 1972-1983, 1983.e1-e11[PMID: 18929564 DOI: 10.1053/j.gastro.2008.08.008]
12. Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A, Weinberg RA. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 2008; 40: 499-507[PMID: 18443585 DOI: 10.1038/ng.127]
13. Sarig R, Rivlin N, Brosh R, Bornstein C, Kamer I, Ezra O, Molchadsky A, Goldfnger N, Brenner O, Rotter V. Mutant p53 facilitates somatic cell reprogramming and augments the malignant potential of reprogrammed cells. J Exp Med 2010; 207: 2127-2140[PMID: 20696700 DOI: 10.1084/jem.20100797]
14. Pece S, Tosoni D, Confalonieri S, Mazzarol G, Vecchi M, Ronzoni S, Bernard L, Viale G, Pelicci PG, Di Fiore PP. Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell 2010; 140: 62-73[PMID: 20074520 DOI: 10.1016/j.cell.2009.12.007]
15. Nowell PC. The clonal evolution of tumor cell populations. Science 1976; 194: 23-28[PMID: 959840]
16. Park CH, Bergsagel DE, McCulloch EA. Mouse myeloma tumor stem cells: a primary cell culture assay. J Natl Cancer Inst 1971; 46: 411-422[PMID: 5115909]
17. Lobo NA, Shimono Y, Qian D, Clarke MF. The biology of cancer stem cells. Annu Rev Cell Dev Biol 2007; 23: 675-699[PMID: 17645413 DOI: 10.1146/annurev.cell-bio.22.010305.104154]
18. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Cace-res-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994; 367: 645-648[PMID: 7509044 DOI: 10.1038/367645a0]
19. Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 2008; 8: 755-768[PMID: 18784658 DOI: 10.1038/nrc2499]
20. Chiou SH, Yu CC, Huang CY, Lin SC, Liu CJ, Tsai TH, Chou SH, Chien CS, Ku HH, Lo JF. Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma. Clin Cancer Res 2008; 14: 4085-4095[PMID: 18593985 DOI: 10.1158/1078-0432.CCR-07-4404]
21. Chen YC, Hsu HS, Chen YW, Tsai TH, How CK, Wang CY, Hung SC, Chang YL, Tsai ML, Lee YY, Ku HH, Chiou SH. Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells. PLoS One 2008; 3: e2637[PMID: 18612434 DOI: 10.1371/journal. pone.0002637]
22. Nagata T, Shimada Y, Sekine S, Hori R, Matsui K, Okumura T, Sawada S, Fukuoka J, Tsukada K. Prognostic signifcance of NANOG and KLF4 for breast cancer. Breast Cancer 2012 Apr 17; Epub ahead of print[PMID: 22528804 DOI: 10.1007/ s12282-012-0357-y]
23. Leis O, Eguiara A, Lopez-Arribillaga E, Alberdi MJ, Her-nandez-Garcia S, Elorriaga K, Pandiella A, Rezola R, Martin AG. Sox2 expression in breast tumours and activation in breast cancer stem cells. Oncogene 2012; 31: 1354-1365[PMID: 21822303 DOI: 10.1038/onc.2011.338]
24. Liu CG, Lu Y, Wang BB, Zhang YJ, Zhang RS, Lu Y, Chen B, Xu H, Jin F, Lu P. Clinical implications of stem cell gene Oct-4 expression in breast cancer. Ann Surg 2011; 253: 1165-1171[PMID: 21394007 DOI: 10.1097/SLA.0b013e318214c54e]
25. Meng HM, Zheng P, Wang XY, Liu C, Sui HM, Wu SJ, Zhou J, Ding YQ, Li JM. Overexpression of nanog predicts tumor progression and poor prognosis in colorectal cancer. Cancer Biol Ther 2010 Feb 16; Epub ahead of print[PMID: 20026903]
26. Saigusa S, Tanaka K, Toiyama Y, Yokoe T, Okugawa Y, Ioue Y, Miki C, Kusunoki M. Correlation of CD133, OCT4, and SOX2 in rectal cancer and their association with distant recurrence after chemoradiotherapy. Ann Surg Oncol 2009; 16: 3488-3498[PMID: 19657699 DOI: 10.1245/s10434-009-0617-z]
27. Matsuoka J, Yashiro M, Sakurai K, Kubo N, Tanaka H, Muguruma K, Sawada T, Ohira M, Hirakawa K. Role of the stemness factors sox2, oct3/4, and nanog in gastric carcinoma. J Surg Res 2012; 174: 130-135[PMID: 21227461 DOI: 10.1016/j.jss.2010.11.903]
28. Shan J, Shen J, Liu L, Xia F, Xu C, Duan G, Xu Y, Ma Q, Yang Z, Zhang Q, Ma L, Liu J, Xu S, Yan X, Bie P, Cui Y, Bian XW, Qian C. Nanog regulates self-renewal of cancer stem cells through the insulin-like growth factor pathway in human hepatocellular carcinoma. Hepatology 2012; 56: 1004-1014[PMID: 22473773 DOI: 10.1002/hep.25745]
29. Huang P, Qiu J, Li B, Hong J, Lu C, Wang L, Wang J, Hu Y, Jia W, Yuan Y. Role of Sox2 and Oct4 in predicting survival of hepatocellular carcinoma patients after hepatectomy. Clin Biochem 2011; 44: 582-589[PMID: 21376027 DOI: 10.1016/ j.clinbiochem.2011.02.012]
30. Li Q, Gao Y, Jia Z, Mishra L, Guo K, Li Z, Le X, Wei D, Huang S, Xie K. Dysregulated Krüppel-like factor 4 and vitamin D receptor signaling contribute to progression of hepatocellular carcinoma. Gastroenterology 2012; 143: 799-810. e1-e2[PMID: 22677193 DOI: 10.1053/j.gastro.2012.05.043]
31. Nirasawa S, Kobayashi D, Tsuji N, Kuribayashi K, Wata-nabe N. Diagnostic relevance of overexpressed Nanog gene in early lung cancers. Oncol Rep 2009; 22: 587-591[PMID: 19639208]
32. Sholl LM, Barletta JA, Yeap BY, Chirieac LR, Hornick JL. Sox2 protein expression is an independent poor prognostic indicator in stage I lung adenocarcinoma. Am J Surg Pathol 2010; 34: 1193-1198[PMID: 20631605 DOI: 10.1097/ PAS.0b013e3181e5e024]
33. Zhang XY, Dong QG, Huang JS, Huang AM, Shi CL, Jin B, Sha HF, Feng JX, Geng Q, Zhou J, Xu HL, Han BH. The expression of stem cell-related indicators as a prognostic factor in human lung adenocarcinoma. J Surg Oncol 2010; 102: 856-862[PMID: 20818602 DOI: 10.1002/jso.21718]
34. Shimada Y, Okumura T, Sekine S, Moriyama M, Sawada S, Matsui K, Yoshioka I, Hojo S, Yoshida T, Nagata T, Fukuoka J, Tsukada K. Expression analysis of iPS cell - inductive genes in esophageal squamous cell carcinoma by tissue microar-ray. Anticancer Res 2012; 32: 5507-5514[PMID: 23225459]
35. Wang Q, He W, Lu C, Wang Z, Wang J, Giercksky KE, Nesland JM, Suo Z. Oct3/4 and Sox2 are significantly associated with an unfavorable clinical outcome in human esophageal squamous cell carcinoma. Anticancer Res 2009; 29: 1233-1241[PMID: 19414369]
36. Hamano R, Miyata H, Yamasaki M, Sugimura K, Tanaka K, Kurokawa Y, Nakajima K, Takiguchi S, Fujiwara Y, Mori M, Doki Y. High expression of Lin28 is associated with tumour aggressiveness and poor prognosis of patients in oesophagus cancer. Br J Cancer 2012; 106: 1415-1423[PMID: 22433967 DOI: 10.1038/bjc.2012.90]
37. Cheng L, Thomas A, Roth LM, Zheng W, Michael H, Karim FW. OCT4: a novel biomarker for dysgerminoma of the ovary. Am J Surg Pathol 2004; 28: 1341-1346[PMID: 15371950 DOI: 10.1097/01.pas.0000135528.03942.1f]
38. Lu L, Katsaros D, Shaverdashvili K, Qian B, Wu Y, de la Longrais IA, Preti M, Menato G, Yu H. Pluripotent factor lin-28 and its homologue lin-28b in epithelial ovarian cancer and their associations with disease outcomes and expression of let-7a and IGF-II. Eur J Cancer 2009; 45: 2212-2218[PMID: 19477633 DOI: 10.1016/j.ejca.2009.05.003]
39. Kim JB, Zaehres H, Wu G, Gentile L, Ko K, Sebastiano V, Araúzo-Bravo MJ, Ruau D, Han DW, Zenke M, Schöler HR. Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature 2008; 454: 646-650[PMID: 18594515 DOI: 10.1038/nature07061]
40. Riggi N, Suvà ML, De Vito C, Provero P, Stehle JC, Baumer K, Cironi L, Janiszewska M, Petricevic T, Suvà D, Tercier S, Joseph JM, Guillou L, Stamenkovic I. EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells. Genes Dev 2010; 24: 916-932[PMID: 20382729 DOI: 10.1101/gad.1899710]
41. Chiba T, Zheng YW, Kita K, Yokosuka O, Saisho H, On-odera M, Miyoshi H, Nakano M, Zen Y, Nakanuma Y, Na-kauchi H, Iwama A, Taniguchi H. Enhanced self-renewal capability in hepatic stem/progenitor cells drives cancer initiation. Gastroenterology 2007; 133: 937-950[PMID: 17673212 DOI: 10.1053/j.gastro.2007.06.016]
42. Nagata S, Hirano K, Kanemori M, Sun LT, Tada T. Self-renewal and pluripotency acquired through somatic repro-gramming to human cancer stem cells. PLoS One 2012; 7: e48699PMID: 23144933 DOI: 10.1371/journal.pone.0048699]
43. Liu Y, Clem B, Zuba-Surma EK, El-Naggar S, Telang S, Jen-son AB, Wang Y, Shao H, Ratajczak MZ, Chesney J, Dean DC. Mouse fibroblasts lacking RB1 function form spheres and undergo reprogramming to a cancer stem cell pheno-type. Cell Stem Cell 2009; 4: 336-347[PMID: 19341623 DOI: 10.1016/j.stem.2009.02.015]
44. Chiou SH, Wang ML, Chou YT, Chen CJ, Hong CF, Hsieh WJ, Chang HT, Chen YS, Lin TW, Hsu HS, Wu CW. Co-expression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentia-tion. Cancer Res 2010; 70: 10433-10444[PMID: 21159654 DOI: 10.1158/0008-5472.CAN-10-2638]
45. Kumar SM, Liu S, Lu H, Zhang H, Zhang PJ, Gimotty PA, Guerra M, Guo W, Xu X. Acquired cancer stem cell phenotypes through Oct4-mediated dedifferentiation. On-cogene 2012; 31: 4898-4911[PMID: 22286766 DOI: 10.1038/ onc.2011.656]
46. Su YJ, Lai HM, Chang YW, Chen GY, Lee JL. Direct repro-gramming of stem cell properties in colon cancer cells by CD44. EMBO J 2011; 30: 3186-3199[PMID: 21701559 DOI: 10.1038/emboj.2011.211]
47. Maherali N, Sridharan R, Xie W, Utikal J, Eminli S, Arnold K, Stadtfeld M, Yachechko R, Tchieu J, Jaenisch R, Plath K, Hochedlinger K. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 2007; 1: 55-70[PMID: 18371336 DOI: 10.1016/j.stem.2007.05.014]
48. Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature 2007; 448: 313-317[PMID: 17554338 DOI: 10.1038/nature05934]
49. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fbroblast cultures by defned factors. Cell 2006; 126: 663-676[PMID: 16904174 DOI: 10.1016/j.cell.2006.07.024]
50. Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein BE, Jaenisch R. In vitro repro-gramming of fbroblasts into a pluripotent ES-cell-like state. Nature 2007; 448: 318-324[PMID: 17554336 DOI: 10.1038/na-ture05944]
51. Yuan F, Zhou W, Zou C, Zhang Z, Hu H, Dai Z, Zhang Y. Expression of Oct4 in HCC and modulation to wnt/β-catenin and TGF-β signal pathways. Mol Cell Biochem 2010; 343: 155-162[PMID: 20549546 DOI: 10.1007/s11010-010-0509-3]
52. Lin ZS, Chu HC, Yen YC, Lewis BC, Chen YW. Krüppel-like factor 4, a tumor suppressor in hepatocellular carcinoma cells reverts epithelial mesenchymal transition by suppressing slug expression. PLoS One 2012; 7: e43593[PMID: 22937066 DOI: 10.1371/journal.pone.0043593]
53. Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC, Ngai P, Chu PW, Lam CT, Poon RT, Fan ST. Signifcance of CD90+ cancer stem cells in human liver cancer. Cancer Cell 2008; 13: 153-166[PMID: 18242515 DOI: 10.1016/j.ccr.2008.01.013]
54. Ma S, Chan KW, Hu L, Lee TK, Wo JY, Ng IO, Zheng BJ, Guan XY. Identification and characterization of tumori-genic liver cancer stem/progenitor cells. Gastroenterology 2007; 132: 2542-2556[PMID: 17570225 DOI: 10.1053/ j.gastro.2007.04.025]
55. Sceusi EL, Loose DS, Wray CJ. Clinical implications of DNA methylation in hepatocellular carcinoma. HPB (Oxford) 2011; 13: 369-376[PMID: 21609368 DOI: 10.1111/ j.1477-2574.2011.00303.x]
56. Zhai JM, Yin XY, Hou X, Hao XY, Cai JP, Liang LJ, Zhang LJ. Analysis of the genome-wide DNA methylation profle of side population cells in hepatocellular carcinoma. Dig Dis Sci 2013; 58: 1934-1947[PMID: 23625283 DOI: 10.1007/ s10620-013-2663-4]
57. De Carvalho DD, You JS, Jones PA. DNA methylation and cellular reprogramming. Trends Cell Biol 2010; 20: 609-617[PMID: 20810283 DOI: 10.1016/j.tcb.2010.08.003]
58. Wang XQ, Ongkeko WM, Chen L, Yang ZF, Lu P, Chen KK, Lopez JP, Poon RT, Fan ST. Octamer 4 (Oct4) mediates che-motherapeutic drug resistance in liver cancer cells through a potential Oct4-AKT-ATP-binding cassette G2 pathway. Hepatology 2010; 52: 528-539[PMID: 20683952 DOI: 10.1002/ hep.23692]
59. Wang J, Lu F, Ren Q, Sun H, Xu Z, Lan R, Liu Y, Ward D, Quan J, Ye T, Zhang H. Novel histone demethylase LSD1 inhibitors selectively target cancer cells with pluripotent stem cell properties. Cancer Res 2011; 71: 7238-7249[PMID: 21975933 DOI: 10.1158/0008-5472.CAN-11-0896]
60. Zhang C, Xu Y, Zhao J, Fan L, Jiang G, Li R, Ling Y, Wu M, Wei L. Elevated expression of the stem cell marker CD133 associated with Line-1 demethylation in hepatocellular carcinoma. Ann Surg Oncol 2011; 18: 2373-2380[PMID: 21331808 DOI: 10.1245/s10434-011-1599-1]
61. You H, Ding W, Rountree CB. Epigenetic regulation of cancer stem cell marker CD133 by transforming growth factor-beta. Hepatology 2010; 51: 1635-1644[PMID: 20196115 DOI: 10.1002/hep.23544]
62. Teng IW, Hou PC, Lee KD, Chu PY, Yeh KT, Jin VX, Tseng MJ, Tsai SJ, Chang YS, Wu CS, Sun HS, Tsai KD, Jeng LB, Nephew KP, Huang TH, Hsiao SH, Leu YW. Targeted meth-ylation of two tumor suppressor genes is suffcient to transform mesenchymal stem cells into cancer stem/initiating cells. Cancer Res 2011; 71: 4653-4663[PMID: 21518779 DOI: 10.1158/0008-5472.CAN-10-3418]
63. Ruvkun G. Molecular biology. Glimpses of a tiny RNA world. Science 2001; 294: 797-799[PMID: 11679654 DOI: 10.1126/science.1066315]
64. Suh MR, Lee Y, Kim JY, Kim SK, Moon SH, Lee JY, Cha KY, Chung HM, Yoon HS, Moon SY, Kim VN, Kim KS. Human embryonic stem cells express a unique set of microRNAs. Dev Biol 2004; 270: 488-498[PMID: 15183728 DOI: 10.1016/ j.ydbio.2004.02.019]
65. Judson RL, Babiarz JE, Venere M, Blelloch R. Embryonic stem cell-specific microRNAs promote induced pluripo-tency. Nat Biotechnol 2009; 27: 459-461[PMID: 19363475 DOI: 10.1038/nbt.1535]
66. Anokye-Danso F, Trivedi CM, Juhr D, Gupta M, Cui Z, Tian Y, Zhang Y, Yang W, Gruber PJ, Epstein JA, Morrisey EE. Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell 2011; 8: 376-388[PMID: 21474102 DOI: 10.1016/ j.stem.2011.03.001]
67. Miyoshi N, Ishii H, Nagano H, Haraguchi N, Dewi DL, Kano Y, Nishikawa S, Tanemura M, Mimori K, Tanaka F, Saito T, Nishimura J, Takemasa I, Mizushima T, Ikeda M, Yamamoto H, Sekimoto M, Doki Y, Mori M. Reprogram-ming of mouse and human cells to pluripotency using mature microRNAs. Cell Stem Cell 2011; 8: 633-638[PMID: 21620789 DOI: 10.1016/j.stem.2011.05.001]
68. Card DA, Hebbar PB, Li L, Trotter KW, Komatsu Y, Mishina Y, Archer TK. Oct4/Sox2-regulated miR-302 targets cyclin D1 in human embryonic stem cells. Mol Cell Biol 2008; 28: 6426-6438[PMID: 18710938 DOI: 10.1128/MCB.00359-08]
69. Khalili M, Sadeghizadeh M, Ghorbanian K, Malekzadeh R, Vasei M, Mowla SJ. Down-regulation of miR-302b, an ESC-specifc microRNA, in Gastric Adenocarcinoma. Cell J 2012; 13: 251-258[PMID: 23508453]
70. Li R, Qian N, Tao K, You N, Wang X, Dou K. MicroRNAs involved in neoplastic transformation of liver cancer stem cells. J Exp Clin Cancer Res 2010; 29: 169[PMID: 21176238 DOI: 10.1186/1756-9966-29-169]
71. Jia Y, Liu H, Zhuang Q, Xu S, Yang Z, Li J, Lou J, Zhang W. Tumorigenicity of cancer stem-like cells derived from hepa-tocarcinoma is regulated by microRNA-145. Oncol Rep 2012; 27: 1865-1872[PMID: 22378186 DOI: 10.3892/or.2012.1701]
72. Yan H, Dong X, Zhong X, Ye J, Zhou Y, Yang X, Shen J, Zhang J. Inhibitions of epithelial to mesenchymal transition and cancer stem cells-like properties are involved in miR-148a-mediated anti-metastasis of hepatocellular carcinoma. Mol Carcinog 2013 Jul 17; Epub ahead of print[PMID: 23861222 DOI: 10.1002/mc.22064]
73. Ji J, Yamashita T, Budhu A, Forgues M, Jia HL, Li C, Deng C, Wauthier E, Reid LM, Ye QH, Qin LX, Yang W, Wang HY, Tang ZY, Croce CM, Wang XW. Identification of microR-NA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells. Hepatology 2009; 50: 472-480[PMID: 19585654 DOI: 10.1002/hep.22989]
74. Yoshida Y, Takahashi K, Okita K, Ichisaka T, Yamanaka S. Hypoxia enhances the generation of induced pluripotent stem cells. Cell Stem Cell 2009; 5: 237-241[PMID: 19716359 DOI: 10.1016/j.stem.2009.08.001]
75. van Malenstein H, Gevaert O, Libbrecht L, Daemen A, Al-lemeersch J, Nevens F, Van Cutsem E, Cassiman D, De Moor B, Verslype C, van Pelt J. A seven-gene set associated with chronic hypoxia of prognostic importance in hepatocel-lular carcinoma. Clin Cancer Res 2010; 16: 4278-4288[PMID: 20592013 DOI: 10.1158/1078-0432.CCR-09-3274]
76. Botchkina IL, Rowehl RA, Rivadeneira DE, Karpeh MS, Crawford H, Dufour A, Ju J, Wang Y, Leyfman Y, Botchkina GI. Phenotypic subpopulations of metastatic colon cancer stem cells: genomic analysis. Cancer Genomics Proteomics 2009; 6: 19-29[PMID: 19451087]
77. Casetti L, Martin-Lannerée S, Najjar I, Plo I, Augé S, Roy L, Chomel JC, Lauret E, Turhan AG, Dusanter-Fourt I. Differential contributions of STAT5A and STAT5B to stress protection and tyrosine kinase inhibitor resistance of chronic myeloid leukemia stem/progenitor cells. Cancer Res 2013; 73: 2052-2058[PMID: 23400594 DOI: 10.1158/0008-5472. CAN-12-3955]
78. Rountree CB, Senadheera S, Mato JM, Crooks GM, Lu SC. Expansion of liver cancer stem cells during aging in methio-nine adenosyltransferase 1A-defcient mice. Hepatology 2008; 47: 1288-1297[PMID: 18167064 DOI: 10.1002/hep.22141]
79. Mathieu J, Zhang Z, Zhou W, Wang AJ, Heddleston JM, Pinna CM, Hubaud A, Stadler B, Choi M, Bar M, Tewari M, Liu A, Vessella R, Rostomily R, Born D, Horwitz M, Ware C, Blau CA, Cleary MA, Rich JN, Ruohola-Baker H. HIF induces human embryonic stem cell markers in cancer cells. Cancer Res 2011; 71: 4640-4652[PMID: 21712410 DOI: 10.1158/0008-5472.CAN-10-3320]
80. Haraguchi N, Ishii H, Mimori K, Tanaka F, Ohkuma M, Kim HM, Akita H, Takiuchi D, Hatano H, Nagano H, Barnard GF, Doki Y, Mori M. CD13 is a therapeutic target in human liver cancer stem cells. J Clin Invest 2010; 120: 3326-3339[PMID: 20697159 DOI: 10.1172/JCI42550]
81. Tang Y, Kitisin K, Jogunoori W, Li C, Deng CX, Mueller SC, Ressom HW, Rashid A, He AR, Mendelson JS, Jessup JM, Shetty K, Zasloff M, Mishra B, Reddy EP, Johnson L, Mishra L. Progenitor/stem cells give rise to liver cancer due to aberrant TGF-beta and IL-6 signaling. Proc Natl Acad Sci USA 2008; 105: 2445-2450[PMID: 18263735 DOI: 10.1073/ pnas.0705395105]
82. Meng F, Glaser SS, Francis H, DeMorrow S, Han Y, Passarini JD, Stokes A, Cleary JP, Liu X, Venter J, Kumar P, Priester S, Hubble L, Staloch D, Sharma J, Liu CG, Alpini G. Functional analysis of microRNAs in human hepatocellular cancer stem cells. J Cell Mol Med 2012; 16: 160-173[PMID: 21352471 DOI: 10.1111/j.1582-4934.2011.01282.x]
83. Arzumanyan A, Friedman T, Ng IO, Clayton MM, Lian Z, Feitelson MA. Does the hepatitis B antigen HBx promote the appearance of liver cancer stem cells? Cancer Res 2011; 71: 3701-3708[PMID: 21464043 DOI: 10.1158/0008-5472.CAN-10-3951]
84. Feng B, Ng JH, Heng JC, Ng HH. Molecules that promote or enhance reprogramming of somatic cells to induced plu-ripotent stem cells. Cell Stem Cell 2009; 4: 301-312[PMID: 19341620 DOI: 10.1016/j.stem.2009.03.005]
85. Yamashita T, Ji J, Budhu A, Forgues M, Yang W, Wang HY, Jia H, Ye Q, Qin LX, Wauthier E, Reid LM, Minato H, Honda M, Kaneko S, Tang ZY, Wang XW. EpCAM-positive hepato-cellular carcinoma cells are tumor-initiating cells with stem/ progenitor cell features. Gastroenterology 2009; 136: 1012-1024[PMID: 19150350 DOI: 10.1053/j.gastro.2008.12.004]
86. Sato N, Meijer L, Skaltsounis L, Greengard P, Brivanlou AH. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specifc inhibitor. Nat Med 2004; 10: 55-63[PMID: 14702635 DOI: 10.1038/nm979]
87. Cole MF, Johnstone SE, Newman JJ, Kagey MH, Young RA. Tcf3 is an integral component of the core regulatory circuitry of embryonic stem cells. Genes Dev 2008; 22: 746-755[PMID: 18347094 DOI: 10.1101/gad.1642408]
88. Lluis F, Pedone E, Pepe S, Cosma MP. Periodic activation of Wnt/beta-catenin signaling enhances somatic cell repro-gramming mediated by cell fusion. Cell Stem Cell 2008; 3: 493-507[PMID: 18983965 DOI: 10.1016/j.stem.2008.08.017]
89. Yamashita T, Budhu A, Forgues M, Wang XW. Activation of hepatic stem cell marker EpCAM by Wnt-beta-catenin signaling in hepatocellular carcinoma. Cancer Res 2007; 67: 10831-10839[PMID: 18006828 DOI: 10.1158/0008-5472. CAN-07-0908]
90. Yang W, Yan HX, Chen L, Liu Q, He YQ, Yu LX, Zhang SH, Huang DD, Tang L, Kong XN, Chen C, Liu SQ, Wu MC, Wang HY. Wnt/beta-catenin signaling contributes to activation of normal and tumorigenic liver progenitor cells. Cancer Res 2008; 68: 4287-4295[PMID: 18519688 DOI: 10.1158/0008-5472.CAN-07-6691]
91. Ichida JK, Blanchard J, Lam K, Son EY, Chung JE, Egli D, Loh KM, Carter AC, Di Giorgio FP, Koszka K, Huangfu D, Akutsu H, Liu DR, Rubin LL, Eggan K. A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog. Cell Stem Cell 2009; 5: 491-503[PMID: 19818703 DOI: 10.1016/j.stem.2009.09.012]
92. Chen CL, Tsukamoto H, Liu JC, Kashiwabara C, Feldman D, Sher L, Dooley S, French SW, Mishra L, Petrovic L, Jeong JH, Machida K. Reciprocal regulation by TLR4 and TGF-β in tumor-initiating stem-like cells. J Clin Invest 2013; 123: 2832-2849[PMID: 23921128 DOI: 10.1172/JCI65859]
93. Burdon T, Stracey C, Chambers I, Nichols J, Smith A. Suppression of SHP-2 and ERK signalling promotes self-renewal of mouse embryonic stem cells. Dev Biol 1999; 210: 30-43[PMID: 10364425 DOI: 10.1006/dbio.1999.9265]
94. Silva J, Barrandon O, Nichols J, Kawaguchi J, Theunissen TW, Smith A. Promotion of reprogramming to ground state pluripotency by signal inhibition. PLoS Biol 2008; 6: e253[PMID: 18942890 DOI: 10.1371/journal.pbio.0060253]
95. Tang KH, Ma S, Lee TK, Chan YP, Kwan PS, Tong CM, Ng IO, Man K, To KF, Lai PB, Lo CM, Guan XY, Chan KW. CD133(+) liver tumor-initiating cells promote tumor angio-genesis, growth, and self-renewal through neurotensin/in-terleukin-8/CXCL1 signaling. Hepatology 2012; 55: 807-820[PMID: 21994122 DOI: 10.1002/hep.24739]
96. Piao LS, Hur W, Kim TK, Hong SW, Kim SW, Choi JE, Sung PS, Song MJ, Lee BC, Hwang D, Yoon SK. CD133+ liver cancer stem cells modulate radioresistance in human hepa-tocellular carcinoma. Cancer Lett 2012; 315: 129-137[PMID: 22079466 DOI: 10.1016/j.canlet.2011.10.012]
97. Ding W, Mouzaki M, You H, Laird JC, Mato J, Lu SC, Roun-tree CB. CD133+ liver cancer stem cells from methionine ad-enosyl transferase 1A-defcient mice demonstrate resistance to transforming growth factor (TGF)-beta-induced apop-tosis. Hepatology 2009; 49: 1277-1286[PMID: 19115422 DOI: 10.1002/hep.22743]
98. Chiba T, Miyagi S, Saraya A, Aoki R, Seki A, Morita Y, Yo-nemitsu Y, Yokosuka O, Taniguchi H, Nakauchi H, Iwama A. The polycomb gene product BMI1 contributes to the maintenance of tumor-initiating side population cells in he-patocellular carcinoma. Cancer Res 2008; 68: 7742-7749[PMID: 18829528 DOI: 10.1158/0008-5472.CAN-07-5882]
99. Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2002; 2: 48-58[PMID: 11902585 DOI: 10.1038/nrc706]
100. Zheng YW, Tsuchida T, Taniguchi H. A novel concept of identifying precancerous cells to enhance anti-cancer therapies. J Hepatobiliary Pancreat Sci 2012; 19: 621-625[PMID: 22878837 DOI: 10.1007/s00534-012-0546-2]
101. Fragola G, Germain PL, Laise P, Cuomo A, Blasimme A, Gross F, Signaroldi E, Bucci G, Sommer C, Pruneri G, Maz-zarol G, Bonaldi T, Mostoslavsky G, Casola S, Testa G. Cell reprogramming requires silencing of a core subset of poly-comb targets. PLoS Genet 2013; 9: e1003292[PMID: 23468641 DOI: 10.1371/journal.pgen.1003292]
102. Chiba T, Suzuki E, Negishi M, Saraya A, Miyagi S, Konuma T, Tanaka S, Tada M, Kanai F, Imazeki F, Iwama A, Yokosu-ka O. 3-Deazaneplanocin A is a promising therapeutic agent for the eradication of tumor-initiating hepatocellular carcinoma cells. Int J Cancer 2012; 130: 2557-2567[PMID: 21717453 DOI: 10.1002/ijc.26264]
103. Choi YJ, Lin CP, Ho JJ, He X, Okada N, Bu P, Zhong Y, Kim SY, Bennett MJ, Chen C, Ozturk A, Hicks GG, Hannon GJ, He L. miR-34 miRNAs provide a barrier for somatic cell reprogramming. Nat Cell Biol 2011; 13: 1353-1360PMID: 22020437 DOI: 10.1038/ncb2366]
104. Zhang J, Luo N, Luo Y, Peng Z, Zhang T, Li S. microR-NA-150 inhibits human CD133-positive liver cancer stem cells through negative regulation of the transcription factor c-Myb. Int J Oncol 2012; 40: 747-756[PMID: 22025269 DOI: 10.3892/ijo.2011.1242]
105. Ma S, Tang KH, Chan YP, Lee TK, Kwan PS, Castilho A, Ng I, Man K, Wong N, To KF, Zheng BJ, Lai PB, Lo CM, Chan KW, Guan XY. miR-130b Promotes CD133(+) liver tumor-initiating cell growth and self-renewal via tumor protein 53-induced nuclear protein 1. Cell Stem Cell 2010; 7: 694-707[PMID: 21112564 DOI: 10.1016/j.stem.2010.11.010]
106. Oikawa T, Kamiya A, Zeniya M, Chikada H, Hyuck AD, Yamazaki Y, Wauthier E, Tajiri H, Miller LD, Wang XW, Reid LM, Nakauchi H. Sal-like protein 4 (SALL4), a stem cell biomarker in liver cancers. Hepatology 2013; 57: 1469-1483[PMID: 23175232 DOI: 10.1002/hep.26159]
107. Ma S, Lee TK, Zheng BJ, Chan KW, Guan XY. CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene 2008; 27: 1749-1758[PMID: 17891174 DOI: 10.1038/sj.onc.1210811]
108. Chow EK, Fan LL, Chen X, Bishop JM. Oncogene-specific formation of chemoresistant murine hepatic cancer stem cells. Hepatology 2012; 56: 1331-1341[PMID: 22505225 DOI: 10.1002/hep.25776]
109. Yamashita T, Honda M, Nio K, Nakamoto Y, Yamashita T, Takamura H, Tani T, Zen Y, Kaneko S. Oncostatin m renders epithelial cell adhesion molecule-positive liver cancer stem cells sensitive to 5-Fluorouracil by inducing hepatocytic differentiation. Cancer Res 2010; 70: 4687-4697[PMID: 20484035 DOI: 10.1158/0008-5472.CAN-09-4210]
110. Zhang L, Sun H, Zhao F, Lu P, Ge C, Li H, Hou H, Yan M, Chen T, Jiang G, Xie H, Cui Y, Huang X, Fan J, Yao M, Li J. BMP4 administration induces differentiation of CD133+ hepatic cancer stem cells, blocking their contributions to he-patocellular carcinoma. Cancer Res 2012; 72: 4276-4285[PMID: 22773665 DOI: 10.1158/0008-5472.CAN-12-1013]
111. Ramos-Mejia V, Fraga MF, Menendez P. iPSCs from cancer cells: challenges and opportunities. Trends Mol Med 2012; 18: 245-247[PMID: 22521522 DOI: 10.1016/ j.molmed.2012.04.001]
112. Carette JE, Pruszak J, Varadarajan M, Blomen VA, Gokhale S, Camargo FD, Wernig M, Jaenisch R, Brummelkamp TR. Generation of iPSCs from cultured human malignant cells. Blood 2010; 115: 4039-4042[PMID: 20233975 DOI: 10.1182/ blood-2009-07-231845]
113. Kumano K, Arai S, Hosoi M, Taoka K, Takayama N, Otsu M, Nagae G, Ueda K, Nakazaki K, Kamikubo Y, Eto K, Abu-ratani H, Nakauchi H, Kurokawa M. Generation of induced pluripotent stem cells from primary chronic myelogenous leukemia patient samples. Blood 2012; 119: 6234-6242[PMID: 22592606 DOI: 10.1182/blood-2011-07-367441]
114. Ali N, Allam H, May R, Sureban SM, Bronze MS, Bader T, Umar S, Anant S, Houchen CW. Hepatitis C virus-induced cancer stem cell-like signatures in cell culture and murine tumor xenografts. J Virol 2011; 85: 12292-12303[PMID: 21937640 DOI: 10.1128/JVI.05920-11]
115. Jopling C, Boue S, Izpisua Belmonte JC. Dedifferentiation, transdifferentiation and reprogramming: three routes to regeneration. Nat Rev Mol Cell Biol 2011; 12: 79-89[PMID: 21252997 DOI: 10.1038/nrm3043]
116. Alison MR, Islam S, Lim S. Stem cells in liver regeneration, fbrosis and cancer: the good, the bad and the ugly. J Pathol 2009; 217: 282-298[PMID: 18991329 DOI: 10.1002/path.2453]