Emerging Role of Nanog in Tumorigenesis and Cancer Stem Cells

Overview

Journal Int J Cancer

Specialty Oncology

Date 2013 Dec 31

PMID 24375318

Citations 75

Authors

Luis E Iv Santaliz-Ruiz

Xiujie Xie

Matthew Old

Theodoros N Teknos

Quintin Pan

Affiliations

Soon will be listed here.

Abstract

Nanog is a transcription factor that is well-established as a key regulator of embryonic stem cell (ESC) maintenance. Recent evidence demonstrates that Nanog is dysregulated and intimately involved in promoting tumorigenesis in part through regulation of the cancer stem cell (CSC) population. Elevated Nanog is associated with poorer outcome in numerous epithelial malignancies. Nanog is enriched in CSCs and ablation of Nanog is sufficient to reduce the CSC pool. Nanog has also been implicated to promote chemoresistance and epithelial-mesenchymal transition (EMT). Insight into the Nanog signaling cascade, upstream regulators and downstream effectors, is beginning to emerge but remains to be fully elucidated. This review highlights the current literature on the emerging role of Nanog in tumorigenesis and CSCs.

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References

Palla A, Piazzolla D, Abad M, Li H, Dominguez O, Schonthaler H . Reprogramming activity of NANOGP8, a NANOG family member widely expressed in cancer. Oncogene. 2013; 33(19):2513-9. DOI: 10.1038/onc.2013.196. View

Bourguignon L, Peyrollier K, Xia W, Gilad E . 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(25):17635-51. PMC: 2427357. DOI: 10.1074/jbc.M800109200. View

Siu M, Wong E, Kong D, Chan H, Jiang L, Wong O . 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. 2012; 32(30):3500-9. DOI: 10.1038/onc.2012.363. View

Mathieu J, Zhang Z, Zhou W, Wang A, Heddleston J, Pinna C . HIF induces human embryonic stem cell markers in cancer cells. Cancer Res. 2011; 71(13):4640-52. PMC: 3129496. DOI: 10.1158/0008-5472.CAN-10-3320. View

Tsai L, Yu C, Chang Y, Yu C, Chou M . Markedly increased Oct4 and Nanog expression correlates with cisplatin resistance in oral squamous cell carcinoma. J Oral Pathol Med. 2011; 40(8):621-8. DOI: 10.1111/j.1600-0714.2011.01015.x. View

Bourguignon L, Spevak C, Wong G, Xia W, Gilad E . 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.... J Biol Chem. 2009; 284(39):26533-46. PMC: 2785342. DOI: 10.1074/jbc.M109.027466. View

Noh K, Kim B, Song K, Cho H, Lee Y, Kim J . Nanog signaling in cancer promotes stem-like phenotype and immune evasion. J Clin Invest. 2012; 122(11):4077-93. PMC: 3484451. DOI: 10.1172/JCI64057. View

Liu T, Xu F, Du X, Lai D, Liu T, Zhao Y . Establishment and characterization of multi-drug resistant, prostate carcinoma-initiating stem-like cells from human prostate cancer cell lines 22RV1. Mol Cell Biochem. 2010; 340(1-2):265-73. DOI: 10.1007/s11010-010-0426-5. View

Chang C, Hsu W, Wang C, Chou C, Yen-Ping Kuo M, Lin B . Connective tissue growth factor activates pluripotency genes and mesenchymal-epithelial transition in head and neck cancer cells. Cancer Res. 2013; 73(13):4147-57. DOI: 10.1158/0008-5472.CAN-12-4085. View

10.

Booth H, Holland P . Eleven daughters of NANOG. Genomics. 2004; 84(2):229-38. DOI: 10.1016/j.ygeno.2004.02.014. View

11.

Covello K, Kehler J, Yu H, Gordan J, Arsham A, Hu C . HIF-2alpha regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth. Genes Dev. 2006; 20(5):557-70. PMC: 1410808. DOI: 10.1101/gad.1399906. View

12.

Takaishi S, Okumura T, Tu S, Wang S, Shibata W, Vigneshwaran R . Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells. 2009; 27(5):1006-20. PMC: 2746367. DOI: 10.1002/stem.30. View

13.

Ibrahim E, Babaei-Jadidi R, Saadeddin A, Spencer-Dene B, Hossaini S, Abuzinadah M . Embryonic NANOG activity defines colorectal cancer stem cells and modulates through AP1- and TCF-dependent mechanisms. Stem Cells. 2012; 30(10):2076-87. DOI: 10.1002/stem.1182. View

14.

Shigeishi H, Biddle A, Gammon L, Emich H, Rodini C, Gemenetzidis E . Maintenance of stem cell self-renewal in head and neck cancers requires actions of GSK3β influenced by CD44 and RHAMM. Stem Cells. 2013; 31(10):2073-83. DOI: 10.1002/stem.1418. View

15.

Hsu H, Huang P, Chang Y, Tzao C, Chen Y, Shih H . Cucurbitacin I inhibits tumorigenic ability and enhances radiochemosensitivity in nonsmall cell lung cancer-derived CD133-positive cells. Cancer. 2011; 117(13):2970-85. DOI: 10.1002/cncr.25869. View

16.

Do D, Ueda J, Messerschmidt D, Lorthongpanich C, Zhou Y, Feng B . A genetic and developmental pathway from STAT3 to the OCT4-NANOG circuit is essential for maintenance of ICM lineages in vivo. Genes Dev. 2013; 27(12):1378-90. PMC: 3701193. DOI: 10.1101/gad.221176.113. View

17.

Demircan B, Dyer L, Gerace M, Lobenhofer E, Robertson K, Brown K . Comparative epigenomics of human and mouse mammary tumors. Genes Chromosomes Cancer. 2008; 48(1):83-97. PMC: 2929596. DOI: 10.1002/gcc.20620. View

18.

Jeter C, Liu B, Liu X, Chen X, Liu C, Calhoun-Davis T . NANOG promotes cancer stem cell characteristics and prostate cancer resistance to androgen deprivation. Oncogene. 2011; 30(36):3833-45. PMC: 3140601. DOI: 10.1038/onc.2011.114. View

19.

Li X, Yang X, Zhang G, Wu S, Deng X, Xiao S . Nuclear β-catenin accumulation is associated with increased expression of Nanog protein and predicts poor prognosis of non-small cell lung cancer. J Transl Med. 2013; 11:114. PMC: 3706347. DOI: 10.1186/1479-5876-11-114. View

20.

Wu M, Jan C, Tsay Y, Yu Y, Huang C, Lin S . Elimination of head and neck cancer initiating cells through targeting glucose regulated protein78 signaling. Mol Cancer. 2010; 9:283. PMC: 2987982. DOI: 10.1186/1476-4598-9-283. View