title: Targeting cancer stem cells: emerging role of Nanog transcription factor.
abstract: The involvement of stemness factors in cancer initiation and progression has drawn much attention recently, especially after the finding that introducing four stemness factors in somatic cells is able to reprogram the cells back to an embryonic stem cell-like state. Following accumulating data revealing abnormal elevated expression levels of key stemness factors, like Nanog, Oct4, and Sox2, in several types of cancer stem cells; the importance and therapeutic potential of targeting these stemness regulators in cancers has turned to research focus. Nanog determines cell fate in both embryonic and cancer stem cells; activating Nanog at an inappropriate time would result in cancer stem cells rather than normal pluripotent stem cells or differentiated somatic cells. Upregulated Nanog is correlated with poor survival outcome of patients with various types of cancer. The discoveries of downstream regulatory pathways directly or indirectly mediated by Nanog indicate that Nanog regulates several aspects of cancer development such as tumor cell proliferation, self-renewal, motility, epithelial-mesenchymal transition, immune evasion, and drug-resistance, which are all defined features for cancer stem cells. The current review paper illustrates the central role of Nanog in the regulatory networks of cancer malignant development and stemness acquirement, as well as in the communication between cancer cells and the surrounding stroma. Though a more defined model is needed to test the therapeutic efficacy of targeting Nanog as a cancer treatment method, current animal experiments using siNanog or shNanog have shown the promising therapeutic potential of Nanog targeting in several types of cancer.
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang Ming University, Taipei, Taiwan.
authors.forename: Mong-Lien
authors.initials: ML
authors.lastname: Wang
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Wu
keywords: cancer stemness; target therapy
references.citation: J Biol Chem. 2008 Jun 20;283(25):17635-51
references.pmid: 18441325
references.citation: Oncogene. 2013 Jul 25;32(30):3500-9
references.pmid: 22945654
references.citation: Cell Death Differ. 2012 Feb;19(2):232-44
references.pmid: 21720384
references.citation: Cancer Res. 2004 Oct 1;64(19):7011-21
references.pmid: 15466194
references.citation: Histopathology. 2011 Oct;59(4):763-75
references.pmid: 22014056
references.citation: Nat Cell Biol. 2012 Nov;14(11):1139-47
references.pmid: 23103910
references.citation: Genomics. 2004 Aug;84(2):229-38
references.pmid: 15233988
references.citation: Stem Cells Dev. 2009 Sep;18(7):1093-108
references.pmid: 19480567
references.citation: Nature. 2006 Dec 7;444(7120):756-60
references.pmid: 17051156
references.citation: Am J Pathol. 2012 Aug;181(2):652-61
references.pmid: 22683467
references.citation: Stem Cells. 2012 Oct;30(10):2076-87
references.pmid: 22851508
references.citation: Mol Cancer Res. 2009 Mar;7(3):330-8
references.pmid: 19276181
references.citation: Histopathology. 2005 Jul;47(1):48-56
references.pmid: 15982323
references.citation: Biomaterials. 2011 Dec;32(34):9077-88
references.pmid: 21890195
references.citation: Cancer Res. 2008 Jan 15;68(2):425-33
references.pmid: 18199536
references.citation: Oncogene. 2011 Sep 8;30(36):3833-45
references.pmid: 21499299
references.citation: FEBS J. 2013 May;280(9):2027-41
references.pmid: 23461856
references.citation: Mol Cell Biol. 2005 Mar;25(6):2475-85
references.pmid: 15743839
references.citation: Arch Pharm Res. 2010 Jul;33(7):1117-25
references.pmid: 20661723
references.citation: Cell Cycle. 2009 Oct 15;8(20):3274-84
references.pmid: 19770585
references.citation: Ann Surg Oncol. 2009 Dec;16(12):3488-98
references.pmid: 19657699
references.citation: Stem Cells. 2009 May;27(5):993-1005
references.pmid: 19415763
references.citation: Cell Stem Cell. 2012 Oct 5;11(4):477-90
references.pmid: 23040477
references.citation: Cell. 2005 May 6;121(3):335-48
references.pmid: 15882617
references.citation: Int J Oncol. 2013 May;42(5):1533-40
references.pmid: 23467648
references.citation: Exp Ther Med. 2012 Sep;4(3):435-441
references.pmid: 23181114
references.citation: Nature. 2008 Jan 10;451(7175):141-6
references.pmid: 18157115
references.citation: EMBO J. 2010 Aug 4;29(15):2659-74
references.pmid: 20581802
references.citation: Cancer Res. 2013 May 15;73(10):3181-9
references.pmid: 23539445
references.citation: Curr Biol. 2007 Jan 23;17(2):165-72
references.pmid: 17196391
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16281-6
references.pmid: 19805294
references.citation: Cancer Res. 2007 May 15;67(10):4827-33
references.pmid: 17510412
references.citation: Int J Androl. 2011 Aug;34(4 Pt 2):e160-74
references.pmid: 21631526
references.citation: J Cell Biochem. 2009 Apr 15;106(6):1079-89
references.pmid: 19229867
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
references.pmid: 12629218
references.citation: Cancer Res. 2003 Sep 15;63(18):5821-8
references.pmid: 14522905
references.citation: Nature. 2008 Oct 23;455(7216):1124-8
references.pmid: 18806776
references.citation: J Biol Chem. 2007 Mar 2;282(9):6265-73
references.pmid: 17204467
references.citation: Hepatology. 2012 Sep;56(3):1004-14
references.pmid: 22473773
references.citation: Nature. 2007 Jan 4;445(7123):111-5
references.pmid: 17122771
references.citation: Pathobiology. 2010;77(6):283-8
references.pmid: 21266826
references.citation: Stem Cells. 2005 Sep;23(8):1035-43
references.pmid: 15983365
references.citation: Biochem Biophys Res Commun. 2012 May 11;421(3):484-9
references.pmid: 22516749
references.citation: Cell Commun Signal. 2012 Aug 08;10(1):23
references.pmid: 22873932
references.citation: Stem Cells. 2009 Aug;27(8):1760-71
references.pmid: 19544440
references.citation: PLoS One. 2011 Jan 27;6(1):e16478
references.pmid: 21304588
references.citation: Stem Cells. 2013 Feb;31(2):248-58
references.pmid: 23169551
references.citation: Nat Med. 1997 Jul;3(7):730-7
references.pmid: 9212098
references.citation: Oncogene. 2013 Sep 12;32(37):4397-405
references.pmid: 23085761
references.citation: Med Oncol. 2012 Jun;29(2):878-85
references.pmid: 21336986
references.citation: J Biol Chem. 2012 Oct 12;287(42):34970-34978
references.pmid: 22927443
references.citation: Nature. 2009 Aug 27;460(7259):1132-5
references.pmid: 19668191
references.citation: Nature. 2004 Nov 18;432(7015):396-401
references.pmid: 15549107
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):973-8
references.pmid: 17210912
references.citation: Cell Cycle. 2005 Mar;4(3):363-4
references.pmid: 15701975
references.citation: FASEB J. 2008 Oct;22(10):3696-705
references.pmid: 18614581
references.citation: Cancer Res. 2012 Nov 15;72(22):6051-64
references.pmid: 23139208
references.citation: Biochem Biophys Res Commun. 2006 Apr 28;343(1):279-85
references.pmid: 16540082
references.citation: Dig Dis Sci. 2012 Sep;57(9):2340-6
references.pmid: 22562535
references.citation: G3 (Bethesda). 2012 Nov;2(11):1447-57
references.pmid: 23173096
references.citation: Biochem Biophys Res Commun. 2007 Feb 16;353(3):770-5
references.pmid: 17196939
references.citation: EMBO J. 2010 Aug 4;29(15):2646-58
references.pmid: 20581804
references.citation: Cancer. 2005 Nov 15;104(10):2092-8
references.pmid: 16206293
references.citation: Ann Surg Oncol. 2012 Sep;19(9):2877-87
references.pmid: 22461131
references.citation: Nature. 2008 Jan 17;451(7176):345-9
references.pmid: 18202660
references.citation: J Biol Chem. 2012 May 25;287(22):18656-73
references.pmid: 22493428
references.citation: Cell Stem Cell. 2011 Jul 8;9(1):50-63
references.pmid: 21726833
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10294-10299
references.pmid: 16801560
references.citation: Stem Cells Dev. 2011 Sep;20(9):1521-8
references.pmid: 21235326
references.citation: Cell Death Differ. 2008 Mar;15(3):504-14
references.pmid: 18049477
references.citation: Nat Rev Cancer. 2008 Oct;8(10):755-68
references.pmid: 18784658
references.citation: Cancer Res. 2012 Apr 1;72(7):1717-27
references.pmid: 22337995
references.citation: EMBO J. 2011 May 18;30(10):1990-2007
references.pmid: 21468029
references.citation: Cancer Res. 2005 Oct 15;65(20):9328-37
references.pmid: 16230395
references.citation: Pathol Int. 2012 Feb;62(2):112-9
references.pmid: 22243781
references.citation: Oncogene. 2012 Jan 12;31(2):149-60
references.pmid: 21685938
references.citation: Nat Cell Biol. 2008 Feb;10(2):194-201
references.pmid: 18223644
references.citation: Blood. 2003 Jan 1;101(1):168-72
references.pmid: 12393704
references.citation: Breast Cancer. 2014 Jan;21(1):96-101
references.pmid: 22528804
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6326-31
references.pmid: 18436640
references.citation: Nature. 1988 Dec 15;336(6200):684-7
references.pmid: 3143916
references.citation: Cancer. 2005 Nov 15;104(10):2255-65
references.pmid: 16228988
references.citation: J Cell Physiol. 2012 Nov;227(11):3678-92
references.pmid: 22378194
references.citation: Leukemia. 2009 May;23(5):925-33
references.pmid: 19148141
references.citation: Stem Cells. 2008 Jul;26(7):1818-30
references.pmid: 18467664
references.citation: Int J Gynecol Pathol. 2011 May;30(3):262-70
references.pmid: 21464727
references.citation: Cell. 2003 May 30;113(5):631-42
references.pmid: 12787504
references.citation: Blood. 1997 Dec 15;90(12):5002-12
references.pmid: 9389720
references.citation: Oncol Rep. 2011 Sep;26(3):593-601
references.pmid: 21573506
references.citation: FEBS J. 2006 Apr;273(8):1723-30
references.pmid: 16623708
references.citation: PLoS One. 2010 Nov 19;5(11):e14062
references.pmid: 21124918
references.citation: Cancer Res. 2006 Feb 15;66(4):1883-90; discussion 1895-6
references.pmid: 16488983
references.citation: Biomaterials. 2012 May;33(14):3693-709
references.pmid: 22361100
references.citation: Nature. 1994 Feb 17;367(6464):645-8
references.pmid: 7509044
references.citation: Eur J Cardiothorac Surg. 2009 Sep;36(3):446-53
references.pmid: 19464919
references.citation: Cell Cycle. 2011 May 1;10(9):1488-98
references.pmid: 21490431
references.citation: PLoS Biol. 2009 Jul;7(7):e1000149
references.pmid: 19582141
references.citation: Gastric Cancer. 2012 Oct;15(4):440-50
references.pmid: 22395309
references.citation: Oncogene. 2006 May 4;25(19):2697-707
references.pmid: 16407845
references.citation: Otol Neurotol. 2012 Dec;33(9):1640-7
references.pmid: 22935817
references.citation: Int J Gynecol Cancer. 2012 Nov;22(9):1489-96
references.pmid: 23095773
references.citation: J Cancer Res Clin Oncol. 2012 Oct;138(10):1759-67
references.pmid: 22714588
references.citation: Nature. 2006 Nov 16;444(7117):364-8
references.pmid: 17093407
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15178-83
references.pmid: 14645703
references.citation: FEBS Lett. 2012 Sep 21;586(19):3529-35
references.pmid: 22963770
references.citation: Cancer Biol Ther. 2010 Feb;9(4):295-302
references.pmid: 20026903
references.citation: Breast Cancer Res. 2008;10(2):R25
references.pmid: 18366788
references.citation: Stem Cells. 2012 Sep;30(9):1842-51
references.pmid: 22696497
references.citation: PLoS One. 2012;7(2):e32459
references.pmid: 22384257
references.citation: Anticancer Agents Med Chem. 2013 May;13(4):576-80
references.pmid: 22934707
references.citation: Nat Genet. 2000 Apr;24(4):372-6
references.pmid: 10742100
references.citation: Nature. 2007 Jan 4;445(7123):106-10
references.pmid: 17122772
references.citation: Acta Histochem. 2013 May;115(4):330-8
references.pmid: 23092806
references.citation: J Oral Pathol Med. 2011 Sep;40(8):621-8
references.pmid: 21342274
references.citation: Exp Mol Med. 2005 Jun 30;37(3):250-4
references.pmid: 16000880
references.citation: Mol Cell. 2012 Jul 27;47(2):169-82
references.pmid: 22795133
references.citation: Int J Nanomedicine. 2012;7:1575-86
references.pmid: 22619514
references.citation: Development. 2011 Nov;138(22):4853-65
references.pmid: 22028025
references.citation: Cell Res. 2007 Jan;17(1):42-9
references.pmid: 17211451
references.citation: Cancer Res. 2010 Dec 15;70(24):10433-44
references.pmid: 21159654
references.citation: J Clin Invest. 2012 Nov;122(11):4077-93
references.pmid: 23093782
references.citation: Cell Physiol Biochem. 2012;30(4):943-52
references.pmid: 23221432
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1548-53
references.pmid: 19171902
references.citation: Mol Cell Biol. 2008 Oct;28(19):5986-95
references.pmid: 18662995
references.citation: Stem Cells. 2012 Dec;30(12):2645-56
references.pmid: 22968989
references.citation: Biochem Biophys Res Commun. 2011 Aug 19;412(1):175-81
references.pmid: 21810410
references.citation: Clin Cancer Res. 2008 Jul 1;14(13):4085-95
references.pmid: 18593985
references.citation: Mol Cell Biochem. 2011 May;351(1-2):109-16
references.pmid: 21246261
references.citation: Nat Cell Biol. 2005 Feb;7(2):165-71
references.pmid: 15619621
references.citation: Science. 2007 Dec 21;318(5858):1917-20
references.pmid: 18029452
references.citation: Stem Cells. 2008 Jan;26(1):17-29
references.pmid: 17916804
references.citation: Cancer Lett. 2012 Aug 1;321(1):80-8
references.pmid: 22381696
references.citation: Pancreas. 2010 Jul;39(5):622-6
references.pmid: 20173672
references.citation: Cell. 2003 May 30;113(5):643-55
references.pmid: 12787505
references.citation: J Control Release. 2012 Apr 30;159(2):240-50
references.pmid: 22285547