Concise Review: NANOG in Cancer Stem Cells and Tumor Development: An Update and Outstanding Questions

Stem Cells

Volumn 33, Issue 8, 2015, Pages 2381-2390

  Jeter, Collene R ^a   Yang, Tao ^b   Wang, Junchen ^b   Chao, Hsueh Ping ^a   Tang, Dean G ^a,b  

^a UNIVERSITY OF TEXAS   (United States)

^b TONGJI UNIVERSITY SCHOOL OF MEDICINE   (China)

Author keywords

Cancer stem cells; NANOG; Self renewal; Tumor development

Indexed keywords

TRANSCRIPTION FACTOR NANOG; HOMEODOMAIN PROTEIN; NANOG PROTEIN, HUMAN; TUMOR PROTEIN;

ARTICLE; BIOLOGICAL ACTIVITY; BREAST CANCER; CANCER DIAGNOSIS; CANCER PROGNOSIS; CANCER STEM CELL; CARCINOGENESIS; CELL FATE; CELL PROLIFERATION; CELL RENEWAL; CHROMATIN ASSEMBLY AND DISASSEMBLY; COLORECTAL CANCER; GLIOBLASTOMA; HUMAN; LEUKEMIA; LIVER CELL CARCINOMA; LUNG CANCER; NONHUMAN; NUCLEAR REPROGRAMMING; OPEN READING FRAME; OVARY CANCER; PANCREAS CANCER; PROMOTER REGION; PROSTATE CANCER; PROTEIN EXPRESSION; PROTEIN FUNCTION; RESTRICTION FRAGMENT LENGTH POLYMORPHISM; TREATMENT OUTCOME; TREATMENT RESPONSE; ANIMAL; CELL TRANSFORMATION; METABOLISM; NEOPLASM; PATHOLOGY;

ANIMALS; CELL TRANSFORMATION, NEOPLASTIC; CELLULAR REPROGRAMMING; HOMEODOMAIN PROTEINS; HUMANS; NANOG HOMEOBOX PROTEIN; NEOPLASM PROTEINS; NEOPLASMS; NEOPLASTIC STEM CELLS;

EID: 84937637639     PISSN: 10665099     EISSN: 15494918     Source Type: Journal    
DOI: 10.1002/stem.2007     Document Type: Article

References (83)

1. Torres-Padilla ME, Chambers I,. Transcription factor heterogeneity in pluripotent stem cells: A stochastic advantage. Development 2014; 141: 2173-2181.
2. Yu J, Vodyanik MA, Smuga-Otto K, et al., Induced pluripotent stem cell lines derived from human somatic cells. Science 2007; 318: 1917-1920.
3. Park IH, Zhao R, West JA, et al., Reprogramming of human somatic cells to pluripotency with defined factors. Nature 2008; 451: 141-146.
4. Takahashi K, Yamanaka S,. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663-676.
5. Gangemi RM, Griffero F, Marubbi D, et al., SOX2 silencing in glioblastoma tumor-initiating cells causes stop of proliferation and loss of tumorigenicity. Stem Cells 2009; 27: 40-48.
6. Leis O, Eguiara A, Lopez-Arribillaga E, et al., Sox2 expression in breast tumours and activation in breast cancer stem cells. Oncogene 2012; 31: 1354-1365.
7. Riggi N, Suva ML, De Vito C, et al., 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.
8. Zhang J, Wang X, Chen B, et al., Expression of Nanog gene promotes NIH3T3 cell proliferation. Biochem Biophys Res Commun 2005; 338: 1098-1102.
9. Piestun D, Kochupurakkal BS, Jacob-Hirsch J, et al., Nanog transforms NIH3T3 cells and targets cell-type restricted genes. Biochem Biophys Res Commun 2006; 343: 279-285.
10. Liu Y, Clem B, Zuba-Surma EK, et al., Mouse fibroblasts lacking RB1 function form spheres and undergo reprogramming to a cancer stem cell phenotype. Cell Stem Cell 2009; 4: 336-347.
11. Lin YL, Han ZB, Xiong FY, et al., Malignant transformation of 293 cells induced by ectopic expression of human Nanog. Mol Cell Biochem 2011; 351: 109-116.
12. Hochedlinger K, Yamada Y, Beard C, et al., Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell 2005; 121: 465-477.
13. Fischedick G, Wu G, Adachi K, et al., Nanog induces hyperplasia without initiating tumors. Stem Cell Res 2014; 13: 300-315.
14. Piazzolla D, Palla AR, Pantoja C, et al., Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia. Nat Commun 2014; 5: 4226.
15. Badeaux MA, Jeter CR, Gong S, et al., In vivo functional studies of tumor-specific retrogene NanogP8 in transgenic animals. Cell Cycle 2013; 12: 2395-2408.
16. Lu X, Mazur SJ, Lin T, et al., The pluripotency factor nanog promotes breast cancer tumorigenesis and metastasis. Oncogene 2014; 33: 2655-2664.
17. Scerbo P, Markov GV, Vivien C, et al., On the origin and evolutionary history of NANOG. PLoS One 2014; 9: e85104.
18. Booth HA, Holland PW,. Eleven daughters of NANOG. Genomics 2004; 84: 229-238.
19. Hart AH, Hartley L, Ibrahim M, et al., Identification, cloning and expression analysis of the pluripotency promoting Nanog genes in mouse and human. Dev Dyn 2004; 230: 187-198.
20. Ambady S, Malcuit C, Kashpur O, et al., Expression of NANOG and NANOGP8 in a variety of undifferentiated and differentiated human cells. Int J Dev Biol 2010; 54: 1743-1754.
21. Fairbanks DJ, Fairbanks AD, Ogden TH, et al., NANOGP8: Evolution of a human-specific retro-oncogene. G3 (Bethesda) 2012; 2: 1447-1457.
22. Zhang J, Espinoza LA, Kinders RJ, et al., NANOG modulates stemness in human colorectal cancer. Oncogene 2013; 32: 4397-4405.
23. Ibrahim EE, Babaei-Jadidi R, Saadeddin A, et al., Embryonic NANOG activity defines colorectal cancer stem cells and modulates through AP1- and TCF-dependent mechanisms. Stem Cells 2012; 30: 2076-2087.
24. Ishiguro T, Sato A, Ohata H, et al., Differential expression of nanog1 and nanogp8 in colon cancer cells. Biochem Biophys Res Commun 2012; 418: 199-204.
25. Jeter CR, Badeaux M, Choy G, et al., Functional evidence that the self-renewal gene NANOG regulates human tumor development. Stem Cells 2009; 27: 993-1005.
26. Uchino K, Hirano G, Hirahashi M, et al., Human Nanog pseudogene8 promotes the proliferation of gastrointestinal cancer cells. Exp Cell Res 2012; 318: 1799-1807.
27. Zhang J, Wang X, Li M, et al., NANOGP8 is a retrogene expressed in cancers. FEBS J 2006; 273: 1723-1730.
28. Lee TK, Castilho A, Cheung VC, et al., CD24(+) liver tumor-initiating cells drive self-renewal and tumor initiation through STAT3-mediated NANOG regulation. Cell Stem Cell 2011; 9: 50-63.
29. Wang J, Levasseur DN, Orkin SH,. Requirement of Nanog dimerization for stem cell self-renewal and pluripotency. Proc Natl Acad Sci USA 2008; 105: 6326-6331.
30. Palla AR, Piazzolla D, Abad M, et al., Reprogramming activity of NANOGP8, a NANOG family member widely expressed in cancer. Oncogene 2014; 33: 2513-2519.
31. Liu B, Badeaux MD, Choy G, et al., Nanog1 in NTERA-2 and recombinant NanogP8 from somatic cancer cells adopt multiple protein conformations and migrate at multiple M.W species. PLoS One 2014; 9: e90615.
32. Coronado D, Godet M, Bourillot PY, et al., A short G1 phase is an intrinsic determinant of naive embryonic stem cell pluripotency. Stem Cell Res 2013; 10: 118-131.
33. Neganova I, Zhang X, Atkinson S, et al., Expression and functional analysis of G1 to S regulatory components reveals an important role for CDK2 in cell cycle regulation in human embryonic stem cells. Oncogene 2009; 28: 20-30.
34. Zhang X, Neganova I, Przyborski S, 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.
35. Pauklin S, Vallier L,. The cell-cycle state of stem cells determines cell fate propensity. Cell 2013; 155: 135-147.
36. dos Santos RL, Tosti L, Radzisheuskaya A, et al., MBD3/NuRD facilitates induction of pluripotency in a context-dependent manner. Cell Stem Cell 2014; 15: 102-110.
37. Liang J, Wan M, Zhang Y, et al., Nanog and Oct4 associate with unique transcriptional repression complexes in embryonic stem cells. Nat Cell Biol 2008; 10: 731-739.
38. Adamo A, Sese B, Boue S, et al., LSD1 regulates the balance between self-renewal and differentiation in human embryonic stem cells. Nat Cell Biol 2011; 13: 652-659.
39. Newman JJ, Young RA,. Connecting transcriptional control to chromosome structure and human disease. Cold Spring Harb Symp Quant Biol 2010; 75: 227-235.
40. Ang YS, Tsai SY, Lee DF, et al., Wdr5 mediates self-renewal and reprogramming via the embryonic stem cell core transcriptional network. Cell 2011; 145: 183-197.
41. Tsai CC, Su PF, Huang YF, et al., Oct4 and Nanog directly regulate Dnmt1 to maintain self-renewal and undifferentiated state in mesenchymal stem cells. Mol Cell 2012; 47: 169-182.
42. Costa Y, Ding J, Theunissen TW, et al., NANOG-dependent function of TET1 and TET2 in establishment of pluripotency. Nature 2013; 495: 370-374.
43. Lee K, Hamm J, Whitworth K, et al., Dynamics of TET family expression in porcine preimplantation embryos is related to zygotic genome activation and required for the maintenance of NANOG. Dev Biol 2014; 386: 86-95.
44. Bourguignon LY, Peyrollier K, Xia W, et al., Hyaluronan-CD44 interaction activates stem cell marker Nanog, Stat-3-mediated MDR1 gene expression, and ankyrin-regulated multidrug efflux in breast and ovarian tumor cells. J Biol Chem 2008; 283: 17635-17651.
45. Bourguignon LY, Earle C, Wong G, et al., Stem cell marker (Nanog) and Stat-3 signaling promote MicroRNA-21 expression and chemoresistance in hyaluronan/CD44-activated head and neck squamous cell carcinoma cells. Oncogene 2012; 31: 149-160.
46. Zbinden M, Duquet A, Lorente-Trigos A, et al., NANOG regulates glioma stem cells and is essential in vivo acting in a cross-functional network with GLI1 and p53. EMBO J 2010; 29: 2659-2674.
47. Niu CS, Li DX, Liu YH, et al., Expression of NANOG in human gliomas and its relationship with undifferentiated glioma cells. Oncol Rep 2011; 26: 593-601.
48. Xu CX, Xu M, Tan L, et al., MicroRNA miR-214 regulates ovarian cancer cell stemness by targeting p53/Nanog. J Biol Chem 2012; 287: 34970-34978.
49. Jeter CR, Liu B, Liu X, et al., NANOG promotes cancer stem cell characteristics and prostate cancer resistance to androgen deprivation. Oncogene 2011; 30: 3833-3845.
50. Ji W, Jiang Z,. Effect of shRNA-mediated inhibition of Nanog gene expression on the behavior of human gastric cancer cells. Oncol Lett 2013; 6: 367-374.
51. Sato A, Okada M, Shibuya K, et al., Resveratrol promotes proteasome-dependent degradation of Nanog via p53 activation and induces differentiation of glioma stem cells. Stem Cell Res 2013; 11: 601-610.
52. Han J, Zhang F, Yu M, et al., RNA interference-mediated silencing of NANOG reduces cell proliferation and induces G0/G1 cell cycle arrest in breast cancer cells. Cancer Lett 2012; 321: 80-88.
53. Chiou SH, Wang ML, Chou YT, 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.
54. Sun C, Sun L, Jiang K, et al., NANOG promotes liver cancer cell invasion by inducing epithelial-mesenchymal transition through NODAL/SMAD3 signaling pathway. Int J Biochem Cell Biol 2013; 45: 1099-1108.
55. Hasmim M, Noman MZ, Lauriol J, et al., Hypoxia-dependent inhibition of tumor cell susceptibility to CTL-mediated lysis involves NANOG induction in target cells. J Immunol 2011; 187: 4031-4039.
56. Noh KH, Lee YH, Jeon JH, et al., Cancer vaccination drives Nanog-dependent evolution of tumor cells toward an immune-resistant and stem-like phenotype. Cancer Res 2012; 72: 1717-1727.
57. Noh KH, Kim BW, Song KH, et al., Nanog signaling in cancer promotes stem-like phenotype and immune evasion. J Clin Invest 2012; 122: 4077-4093.
58. Hoei-Hansen CE,. Application of stem cell markers in search for neoplastic germ cells in dysgenetic gonads, extragonadal tumours, and in semen of infertile men. Cancer Treat Rev 2008; 34: 348-367.
59. Zhang K, Fowler M, Glass J, et al., Activated 5' flanking region of NANOGP8 in a self-renewal environment is associated with increased sphere formation and tumor growth of prostate cancer cells. Prostate 2014; 74: 381-394.
60. Germann M, Wetterwald A, Guzman-Ramirez N, et al., Stem-like cells with luminal progenitor phenotype survive castration in human prostate cancer. Stem Cells 2012; 30: 1076-1086.
61. Seiler D, Zheng J, Liu G, et al., Enrichment of putative prostate cancer stem cells after androgen deprivation: Upregulation of pluripotency transactivators concurs with resistance to androgen deprivation in LNCaP cell lines. Prostate 2013; 73: 1378-1390.
62. Qin J, Liu X, Laffin B, et al., The PSA(-/lo) prostate cancer cell population harbors self-renewing long-term tumor-propagating cells that resist castration. Cell Stem Cell 2012; 10: 556-569.
63. Toivanen R, Frydenberg M, Murphy D, et al., A preclinical xenograft model identifies castration-tolerant cancer-repopulating cells in localized prostate tumors. Sci Transl Med 2013; 5: 187ra171.
64. Mathieu J, Zhang Z, Zhou W, et al., HIF induces human embryonic stem cell markers in cancer cells. Cancer Res 2011; 71: 4640-4652.
65. Ma Y, Liang D, Liu J, et al., Prostate cancer cell lines under hypoxia exhibit greater stem-like properties. PLoS One 2011; 6: e29170.
66. Shan J, Shen J, Liu L, et al., Nanog regulates self-renewal of cancer stem cells through the insulin-like growth factor pathway in human hepatocellular carcinoma. Hepatology 2012; 56: 1004-1014.
67. Yin X, Li YW, Zhang BH, et al., Coexpression of stemness factors oct4 and nanog predict liver resection. Ann Surg Oncol 2012; 19: 2877-2887.
68. Eberle I, Pless B, Braun M, et al., Transcriptional properties of human NANOG1 and NANOG2 in acute leukemic cells. Nucleic Acids Res 2010; 38: 5384-5395.
69. Cao J, Li L, Chen C, et al., RNA interference-mediated silencing of NANOG leads to reduced proliferation and self-renewal, cell cycle arrest and apoptosis in T-cell acute lymphoblastic leukemia cells via the p53 signaling pathway. Leuk Res 2013; 37: 1170-1177.
70. Higgins DM, Wang R, Milligan B, et al., Brain tumor stem cell multipotency correlates with nanog expression and extent of passaging in human glioblastoma xenografts. Oncotarget 2013; 4: 792-801.
71. Moon JH, Kwon S, Jun EK, et al., Nanog-induced dedifferentiation of p53-deficient mouse astrocytes into brain cancer stem-like cells. Biochem Biophys Res Commun 2011; 412: 175-181.
72. Elsir T, Edqvist PH, Carlson J, et al., A study of embryonic stem cell-related proteins in human astrocytomas: Identification of Nanog as a predictor of survival. Int J Cancer 2014; 134: 1123-1131.
73. Meng HM, Zheng P, Wang XY, et al., Over-expression of Nanog predicts tumor progression and poor prognosis in colorectal cancer. Cancer Biol Ther 2010; 9: 295-302.
74. Xu F, Dai C, Zhang R, et al., Nanog: A potential biomarker for liver metastasis of colorectal cancer. Dig Dis Sci 2012; 57: 2340-2346.
75. Du Y, Ma C, Wang Z, et al., Nanog, a novel prognostic marker for lung cancer. Surg Oncol 2013; 22: 224-229.
76. Nagata T, Shimada Y, Sekine S, et al., Prognostic significance of NANOG and KLF4 for breast cancer. Breast Cancer 2014; 21: 96-101.
77. Bourguignon LY, Spevak CC, Wong G, et al., Hyaluronan-CD44 interaction with protein kinase C(epsilon) promotes oncogenic signaling by the stem cell marker Nanog and the Production of microRNA-21, leading to down-regulation of the tumor suppressor protein PDCD4, anti-apoptosis, and chemotherapy resistance in breast tumor cells. J Biol Chem 2009; 284: 26533-26546.
78. Lu Y, Zhu H, Shan H, et al., Knockdown of Oct4 and Nanog expression inhibits the stemness of pancreatic cancer cells. Cancer Lett 2013; 340: 113-123.
79. Amsterdam A, Raanan C, Schreiber L, et al., LGR5 and Nanog identify stem cell signature of pancreas beta cells which initiate pancreatic cancer. Biochem Biophys Res Commun 2013; 433: 157-162.
80. Zhang S, Balch C, Chan MW, et al., Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res 2008; 68: 4311-4320.
81. Pan Y, Jiao J, Zhou C, et al., Nanog is highly expressed in ovarian serous cystadenocarcinoma and correlated with clinical stage and pathological grade. Pathobiology 2010; 77: 283-288.
82. Siu MK, Wong ES, Kong DS, et al., Stem cell transcription factor NANOG controls cell migration and invasion via dysregulation of E-cadherin and FoxJ1 and contributes to adverse clinical outcome in ovarian cancers. Oncogene 2013; 32: 3500-3509.
83. Liu K, Jiang M, Lu Y, et al., Sox2 cooperates with inflammation-mediated Stat3 activation in the malignant transformation of foregut basal progenitor cells. Cell Stem Cell 2013; 12: 304-315.