Nanog induces hyperplasia without initiating tumors

Stem Cell Research

Volumn 13, Issue 2, 2014, Pages 300-315

  Fischedick, Gerrit ^a,b   Wu, Guangming ^a   Adachi, Kenjiro ^a   Araúzo Bravo, Marcos J ^a,f   Greber, Boris ^a   Radstaak, Martina ^a   Köhler, Gabriele ^d   Tapia, Natalia ^a   Iacone, Roberto ^c,e   Anastassiadis, Konstantinos ^c   Schöler, Hans R ^a,b   Zaehres, Holm ^a  

^a MAX PLANCK INSTITUTE FOR MOLECULAR BIOMEDICINE   (Germany)

^b UNIVERSITY OF MÜNSTER   (Germany)

^c DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^d UNIVERSITY HOSPITAL MÜNSTER   (Germany)

^e F HOFFMANN LA ROCHE LTD   (Switzerland)

^f BASQUE FOUNDATION FOR SCIENCE   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

KRUPPEL LIKE FACTOR 4; TRANSCRIPTION FACTOR CDX2; TRANSCRIPTION FACTOR NANOG; CDX2 PROTEIN, MOUSE; HOMEODOMAIN PROTEIN; KRUPPEL LIKE FACTOR; NANOG PROTEIN, MOUSE; TRANSCRIPTION FACTOR; TUMOR SUPPRESSOR PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CARCINOGENESIS; CELL PROLIFERATION; CHROMATIN IMMUNOPRECIPITATION; COLON MUCOSA; CONTROLLED STUDY; CRYPT CELL; DISEASE ASSOCIATION; DOWN REGULATION; EMBRYO; EMBRYO DEVELOPMENT; FEMALE; HYPERPLASIA; IN VITRO STUDY; INTESTINE EPITHELIUM; INTESTINE VILLUS; MALE; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; COLONIC EPITHELIUM HYPERPLASIA; GENE EXPRESSION; INTESTINAL EPITHELIUM HYPERPLASIA; WNT SIGNALING PATHWAY; 3T3 CELL LINE; ANIMAL; C3H MOUSE; C57BL MOUSE; CELL TRANSFORMATION; COLON; COLON TUMOR; EPITHELIUM CELL; GENE EXPRESSION REGULATION; GENE SILENCING; GENETIC TRANSFECTION; GENETICS; GENOTYPE; INTESTINE MUCOSA; METABOLISM; PATHOLOGY; SIGNAL TRANSDUCTION; SMALL INTESTINE; TIME; TRANSGENIC MOUSE;

ANIMALS; CELL PROLIFERATION; CELL TRANSFORMATION, NEOPLASTIC; COLON; COLONIC NEOPLASMS; EPITHELIAL CELLS; GENE EXPRESSION REGULATION; GENE KNOCKDOWN TECHNIQUES; GENOTYPE; HOMEODOMAIN PROTEINS; HYPERPLASIA; INTESTINAL MUCOSA; INTESTINE, SMALL; KRUPPEL-LIKE TRANSCRIPTION FACTORS; MICE; MICE, INBRED C3H; MICE, INBRED C57BL; MICE, TRANSGENIC; NIH 3T3 CELLS; PHENOTYPE; SIGNAL TRANSDUCTION; TIME FACTORS; TRANSCRIPTION FACTORS; TRANSFECTION; TUMOR SUPPRESSOR PROTEINS;

EID: 84908569724     PISSN: 18735061     EISSN: 18767753     Source Type: Journal    
DOI: 10.1016/j.scr.2014.08.001     Document Type: Article

References (67)

1. Al-Hajj M., Wicha M.S., Benito-Hernandez A., Morrison S.J., Clarke M.F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:3983-3988.
2. Alldridge L., Metodieva G., Greenwood C., Al-Janabi K., Thwaites L., Sauven P., Metodiev M. Proteome profiling of breast tumors by gel electrophoresis and nanoscale electrospray ionization mass spectrometry. J. Proteome Res. 2008, 7:1458-1469.
3. Anastassiadis K., Kim J., Daigle N., Sprengel R., Schöler H.R., Stewart A.F. A predictable ligand regulated expression strategy for stably integrated transgenes in mammalian cells in culture. Gene 2002, 298:159-172.
4. Anastassiadis K., Rostovskaya M., Lubitz S., Weidlich S., Stewart A.F. Precise conditional immortalization of mouse cells using tetracycline-regulated SV40 large T-antigen. Genesis 2010, 48:220-232.
5. Aoki K., Tamai Y., Horiike S., Oshima M., Taketo M.M. Colonic polyposis caused by mTOR-mediated chromosomal instability in Apc+/Delta716 Cdx2+/- compound mutant mice. Nat. Genet. 2003, 35:323-330.
6. Atlasi Y., Mowla S.J., Ziaee S.A.M., Bahrami A.-R. OCT-4, an embryonic stem cell marker, is highly expressed in bladder cancer. Int. J. Cancer 2007, 120:1598-1602.
7. Badeaux M.A., Jeter C.R., Gong S., Liu B., Suraneni M.V., Rundhaug J., Fischer S.M., Yang T., Kusewitt D., Tang D.G. In vivo functional studies of tumor-specific retrogene NanogP8 in transgenic animals. Cell Cycle 2013, 12:2395-2408.
8. Beachy P.A., Karhadkar S.S., Berman D.M. Tissue repair and stem cell renewal in carcinogenesis. Nature 2004, 432:324-331.
9. Beck F., Chawengsaksophak K., Luckett J., Giblett S., Tucci J., Brown J., Poulsom R., Jeffery R., Wright N.A. A study of regional gut endoderm potency by analysis of Cdx2 null mutant chimaeric mice. Dev. Biol. 2003, 255:399-406.
10. Beck F., Chawengsaksophak K., Waring P., Playford R.J., Furness J.B. Reprogramming of intestinal differentiation and intercalary regeneration in Cdx2 mutant mice. Proc. Natl. Acad. Sci. U. S. A. 1999, 96:7318-7323.
11. Ben-Porath I., Thomson M.W., Carey V.J., Ge R., Bell G.W., Regev A., Weinberg R.A. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat. Genet. 2008, 40:499-507.
12. Benahmed F., Gross I., Gaunt S.J., Beck F., Jehan F., Domon Dell C., Martin E., Kedinger M., Freund J.N., Duluc I. Multiple regulatory regions control the complex expression pattern of the mouse Cdx2 homeobox gene. Gastroenterology 2008, 135:1238-1247. (e3).
13. Boiani M., Eckardt S., Schöler H.R., McLaughlin K.J. Oct4 distribution and level in mouse clones: consequences for pluripotency. Genes Dev. 2002, 16:1209-1219.
14. Bonhomme C., Duluc I., Martin E., Chawengsaksophak K., Chenard M.-P., Kedinger M., Beck F., Freund J.-N., Domon-Dell C. The Cdx2 homeobox gene has a tumour suppressor function in the distal colon in addition to a homeotic role during gut development. Gut 2003, 52:1465-1471.
15. Boyer L.A., Lee T.I., Cole M.F., Johnstone S.E., Levine S.S., Zucker J.P., Guenther M.G., Kumar R.M., Murray H.L., Jenner R.G., et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 2005, 122:947-956.
16. Bussolati B., Bruno S., Grange C., Ferrando U., Camussi G. Identification of a tumor-initiating stem cell population in human renal carcinomas. FASEB J. 2008, 22:3696-3705.
17. Camp E., S nchez-S nchez A.V., Garc a-Espa a A., DeSalle R., Odqvist L., Enrique O'Connor J., Mullor J.L. Nanog regulates proliferation during early fish development. Stem Cells 2009, 27:2081-2091.
18. Cantz T., Key G., Bleidissel M., Gentile L., Han D.W., Brenne A., Schöler H.R. Absence of OCT4 expression in somatic tumor cell lines. Stem Cells 2008, 26:692-697.
19. Chambers I., Colby D., Robertson M., Nichols J., Lee S., Tweedie S., Smith A. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 2003, 113:643-655.
20. Chawengsaksophak K., James R., Hammond V.E., Köntgen F., Beck F. Homeosis and intestinal tumours in Cdx2 mutant mice. Nature 1997, 386:84-87.
21. Chen L., Yabuuchi A., Eminli S., Takeuchi A., Lu C.-W., Hochedlinger K., Daley G.Q. Cross-regulation of the Nanog and Cdx2 promoters. Nat. Publ. Group 2009, 19:1052-1061.
22. Chen X., Xu H., Yuan P., Fang F., Huss M., Vega V.B., Wong E., Orlov Y.L., Zhang W., Jiang J., et al. Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 2008, 133:1106-1117.
23. Chiou S.-H., Wang M.-L., Chou Y.-T., Chen C.-J., Hong C.-F., Hsieh W.-J., Chang H.-T., Chen Y.-S., Lin T.-W., Hsu H.-S., et al. Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation. Cancer Res. 2010, 70:10433-10444.
24. Chiou S.-H., Yu C.-C., Huang C.-Y., Lin S.-C., Liu C.-J., Tsai T.-H., Chou S.-H., Chien C.-S., Ku H.-H., Lo J.-F. 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.
25. Dang D.T., Mahatan C.S., Dang L.H., Agboola I.A., Yang V.W. Expression of the gut-enriched Krüppel-like factor (Krüppel-like factor 4) gene in the human colon cancer cell line RKO is dependent on CDX2. Oncogene 2001, 20:4884-4890.
26. Do J.T., Schöler H.R. Nuclei of embryonic stem cells reprogram somatic cells. Stem Cells 2004, 22:941-949.
27. Ee H.C., Erler T., Bhathal P.S., Young G.P., James R.J. Cdx-2 homeodomain protein expression in human and rat colorectal adenoma and carcinoma. Am. J. Pathol. 1995, 147:586-592.
28. Ezeh U.I., Turek P.J., Reijo R.A., Clark A.T. Human embryonic stem cell genes OCT4, NANOG, STELLAR, and GDF3 are expressed in both seminoma and breast carcinoma. Cancer 2005, 104:2255-2265.
29. Gao N., White P., Kaestner K.H. Establishment of intestinal identity and epithelial-mesenchymal signaling by Cdx2. Dev. Cell 2009, 16:588-599.
30. Garrett-Sinha L.A., Eberspaecher H., Seldin M.F., de Crombrugghe B. A gene for a novel zinc-finger protein expressed in differentiated epithelial cells and transiently in certain mesenchymal cells. J. Biol. Chem. 1996, 271:31384-31390.
31. Gillis A.J., Stoop H., Biermann K., van Gurp R.J., Swartzman E., Cribbes S., Ferlinz A., Shannon M., Oosterhuis J.W., Looijenga L.H. Expression and interdependencies of pluripotency factors LIN28, OCT3/4, NANOG and SOX2 in human testicular germ cells and tumours of the testis. Int. J. Androl. 2011, 34(4 Pt 2):e160-e174.
32. Hochedlinger K., Yamada Y., Beard C., Jaenisch R. Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell 2005, 121:465-477.
33. Hubbard S.A., Gargett C.E. A cancer stem cell origin for human endometrial carcinoma?. Reproduction 2010, 140:23-32.
34. Irizarry R.A., Bolstad B.M., Collin F., Cope L.M., Hobbs B., Speed T.P. Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res. 2003, 31:e15.
35. Jeter C.R., Badeaux M., Choy G., Chandra D., Patrawala L., Liu C., Calhoun-Davis T., Zaehres H., Daley G.Q., Tang D.G. Functional evidence that the self-renewal gene NANOG regulates human tumor development. Stem Cells 2009, 27:993-1005.
36. Katz J.P., Perreault N., Goldstein B.G., Actman L., McNally S.R., Silberg D.G., Furth E.E., Kaestner K.H. Loss of Klf4 in mice causes altered proliferation and differentiation and precancerous changes in the adult stomach. Gastroenterology 2005, 128:935-945.
37. Katz J.P., Perreault N., Goldstein B.G., Lee C.S., Labosky P.A., Yang V.W., Kaestner K.H. The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon. Development 2002, 129:2619-2628.
38. Kim J.B., Sebastiano V., Wu G., Araúzo-Bravo M.J., Sasse P., Gentile L., Ko K., Ruau D., Ehrich M., van den Boom D., et al. Oct4-induced pluripotency in adult neural stem cells. Cell 2009, 136:411-419.
39. Kim J.B., Zaehres H., Wu G., Gentile L., Ko K., Sebastiano V., Araúzo-Bravo M.J., Ruau D., Han D.W., Zenke M., et al. Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature 2008, 454:646-650.
40. Lin T., Ding Y.-Q., Li J.-M. Overexpression of Nanog protein is associated with poor prognosis in gastric adenocarcinoma. Med. Oncol. 2012, 29:878-885.
41. Lobo N.A., Shimono Y., Qian D., Clarke M.F. The biology of cancer stem cells. Annu. Rev. Cell Dev. Biol. 2007, 23:675-699.
42. Mahatan C.S., Kaestner K.H., Geiman D.E., Yang V.W. Characterization of the structure and regulation of the murine gene encoding gut-enriched Krüppel-like factor (Krüppel-like factor 4). Nucleic Acids Res. 1999, 27:4562-4569.
43. Marson A., Levine S.S., Cole M.F., Frampton G.M., Brambrink T., Johnstone S., Guenther M.G., Johnston W.K., Wernig M., Newman J., et al. Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell 2008, 134:521-533.
44. Masui S., Nakatake Y., Toyooka Y., Shimosato D., Yagi R., Takahashi K., Okochi H., Okuda A., Matoba R., Sharov A.A., et al. Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat. Cell Biol. 2007, 9:625-635.
45. McConnell B.B., Ghaleb A.M., Nandan M.O., Yang V.W. The diverse functions of Krüppel-like factors 4 and 5 in epithelial biology and pathobiology. Bioessays 2007, 29:549-557.
46. Meng H.-M., Zheng P., Wang X.-Y., Liu C., Sui H.-M., Wu S.-J., Zhou J., Ding Y.-Q., Li J.-M. Overexpression of nanog predicts tumor progression and poor prognosis in colorectal cancer. Cancer Biol. Ther. 2010, 9.
47. Mitsui K., Tokuzawa Y., Itoh H., Segawa K., Murakami M., Takahashi K., Maruyama M., Maeda M., Yamanaka S. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 2003, 113:631-642.
48. Nagy A., Gertsenstein M., Vintersten K., Behringer R. Manipulating the Mouse Embryo: A Laboratory Manual 2002, Cold Spring Harbor Laboratory Press. Third ed.
49. O'Brien C.A., Pollett A., Gallinger S., Dick J.E. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007, 445:106-110.
50. Reya T., Morrison S.J., Clarke M.F., Weissman I.L. Stem cells, cancer, and cancer stem cells. Nature 2001, 414:105-111.
51. Saiki Y., Ishimaru S., Mimori K., Takatsuno Y., Nagahara M., Ishii H., Yamada K., Mori M. Comprehensive analysis of the clinical significance of inducing pluripotent stemness-related gene expression in colorectal cancer cells. Ann. Surg. Oncol. 2009, 16:2638-2644.
52. Shields J.M., Christy R.J., Yang V.W. Identification and characterization of a gene encoding a gut-enriched Krüppel-like factor expressed during growth arrest. J. Biol. Chem. 1996, 271:20009-20017.
53. Stingl J., Caldas C. Molecular heterogeneity of breast carcinomas and the cancer stem cell hypothesis. Nat. Rev. Cancer 2007, 7:791-799.
54. Summers M.C., McGinnis L.K., Lawitts J.A., Raffin M., Biggers J.D. IVF of mouse ova in a simplex optimized medium supplemented with amino acids. Hum. Reprod. 2000, 15:1791-1801.
55. Szabó P.E., Hübner K., Schöler H., Mann J.R. Allele-specific expression of imprinted genes in mouse migratory primordial germ cells. Mech. Dev. 2002, 115:157-160.
56. Tai M.-H., Chang C.-C., Kiupel M., Webster J.D., Olson L.K., Trosko J.E. Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis 2005, 26:495-502.
57. Wang J., Rao S., Chu J., Shen X., Levasseur D.N., Theunissen T.W., Orkin S.H. A protein interaction network for pluripotency of embryonic stem cells. Nature 2006, 444:364-368.
58. Watts J.A., Zhang C., Klein-Szanto A.J., Kormish J.D., Fu J., Zhang M.Q., Zaret K.S. Study of FoxA pioneer factor at silent genes reveals Rfx-repressed enhancer at Cdx2 and a potential indicator of esophageal adenocarcinoma development. PLoS Genet. 2011, 7:e1002277.
59. Wen J., Park J.Y., Park K.H., Chung H.W., Bang S., Park S.W., Song S.Y. Oct4 and Nanog expression is associated with early stages of pancreatic carcinogenesis. Pancreas 2010, 39:622-626.
60. Wong D.J., Liu H., Ridky T.W., Cassarino D., Segal E., Chang H.Y. Module map of stem cell genes guides creation of epithelial cancer stem cells. Cell Stem Cell 2008, 2:333-344.
61. Ye F., Zhou C., Cheng Q., Shen J., Chen H. Stem-cell-abundant proteins Nanog, Nucleostemin and Musashi1 are highly expressed in malignant cervical epithelial cells. BMC Cancer 2008, 8:108.
62. Yoshimizu T., Sugiyama N., De Felice M., Yeom Y.I., Ohbo K., Masuko K., Obinata M., Abe K., Schöler H.R., Matsui Y. Germline-specific expression of the Oct-4/green fluorescent protein (GFP) transgene in mice. Dev. Growth Differ. 1999, 41:675-684.
63. Zhang J., Wang X., Chen B., Suo G., Zhao Y., Duan Z., Dai J. Expression of Nanog gene promotes NIH3T3 cell proliferation. Biochem. Biophys. Res. Commun. 2005, 338:1098-1102.
64. Zhang S., Balch C., Chan M.W., Lai H.-C., Matei D., Schilder J.M., Yan P.S., Huang T.H.-M., Nephew K.P. Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res. 2008, 68:4311-4320.
65. Zhang X., Neganova I., Przyborski S., Yang C., Cooke M., Atkinson S.P., Anyfantis G., Fenyk S., Keith W.N., Hoare S.F., et al. A role for NANOG in G1 to S transition in human embryonic stem cells through direct binding of CDK6 and CDC25A. J. Cell Biol. 2009, 184:67-82.
66. Zhang Y., Buchholz F., Muyrers J.P., Stewart A.F. A new logic for DNA engineering using recombination in Escherichia coli. Nat. Genet. 1998, 20:123-128.
67. Zhang Y., Muyrers J.P., Testa G., Stewart A.F. DNA cloning by homologous recombination in Escherichia coli. Nat. Biotechnol. 2000, 18:1314-1317.