Helicobacter pylori infection, oncogenic pathways and epigenetic mechanisms in gastric carcinogenesis.
Chronic colonization of the human stomach by Helicobacter pylori, a Gram-negative bacterium, is the major cause of chronic gastritis, peptic ulcers and gastric cancer. Recent progress has elucidated important bacterial and host factors that are responsible for H. pylori-induced gastric inflammation and gastric malignancy. H. pylori cytotoxin-associated antigen A is the major oncogenic factor injected into host cells from bacteria and it disrupts epithelial cell functions. Together with H. pylori cag pathogenicity island, it causes general inflammatory stress within gastric mucosa and activates multiple oncogenic pathways in epithelial cells. A growing list of these pathways includes NF-kappaB, activator protein-1, PI3K, signal transducers and activators of transcription 3, Wnt/beta-catenin and cyclooxygenase 2. H. pylori induces epigenetic alterations, such as DNA methylation and histone modification, which play critical roles in oncogenic transformation. In addition, investigations into gastric stem cell or progenitor cell biology have shed light on the mechanisms through which gastric cancer may originate. Continued investigation in these areas will yield novel insights and help to elucidate the mechanisms of bacteria-induced carcinogenesis.
Ding
Song-Ze
SZ
Department of Microbiology, University of Virginia Health System, Charlottesville, VA 22908, USA. song.ding@uky.edu
Goldberg
Joanna B
JB
Hatakeyama
Masanori
M
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D016481:Helicobacter Infections / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D016480:Helicobacter pylori; D006801:Humans; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology*
Cell Microbiol. 2009 Jan;11(1):70-82
18782353
Cancer Cell. 2008 Nov 4;14(5):408-19
18977329
Oncogene. 2007 Jul 12;26(32):4617-26
17237808
Biochem Biophys Res Commun. 2008 May 2;369(2):526-31
18302936
Lancet Oncol. 2008 Feb;9(2):139-48
18207460
Gastroenterology. 2007 Apr;132(4):1309-19
17408661
Ann N Y Acad Sci. 2003 Mar;983:220-31
12724227
Cancer. 2006 Mar 15;106(6):1250-9
16475210
J Immunol. 2006 Dec 1;177(11):7950-8
17114467
Eur J Cancer. 2001 Oct;37 Suppl 8:S4-66
11602373
Clin Cancer Res. 2003 Dec 15;9(17):6410-8
14695142
Cancer Res. 2003 Nov 1;63(21):7068-75
14612497
Gastroenterology. 2006 Oct;131(4):1086-95
17030179
Br J Cancer. 2007 Jul 2;97(1):1-5
17592497
Science. 2004 Nov 26;306(5701):1568-71
15567866
Cancer Res. 2003 Dec 15;63(24):8606-13
14695171
Mol Microbiol. 2001 May;40(4):815-23
11401689
PLoS One. 2010 Apr 01;5(4):e9875
20368982
Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10646-51
16027366
Virchows Arch. 2001 Oct;439(4):512-22
11710638
Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):1003-8
18192401
Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5186-91
15795379
Epigenetics. 2009 Nov 16;4(8):577-86
20081355
Lab Invest. 2008 Mar;88(3):328-36
18180700
Mol Pharmacol. 2004 Dec;66(6):1465-77
15456896
Ann Surg Oncol. 2008 Jul;15(7):1968-76
18470569
Differentiation. 2001 Aug;68(1):13-21
11683489
Nat Med. 2007 Apr;13(4):470-6
17401375
Lab Invest. 2004 Apr;84(4):479-84
14968123
Gastroenterology. 2000 Jan;118(1):36-47
10611152
EMBO J. 2008 Jun 18;27(12):1671-81
18511911
EMBO J. 2003 Feb 3;22(3):515-28
12554652
Ann N Y Acad Sci. 2007 Apr;1100:60-74
17460165
Dig Dis. 2007;25(3):225-9
17827945
Int J Cancer. 2004 Jun 10;110(2):212-8
15069684
Curr Opin Gastroenterol. 2005 Nov;21(6):653-9
16220040
Cancer Sci. 2003 Aug;94(8):692-8
12901794
Science. 2003 May 30;300(5624):1430-4
12775840
Nature. 2007 May 17;447(7142):330-3
17507984
J Infect Dis. 2009 Mar 1;199(5):641-51
19199544
Nature. 1997 Aug 7;388(6642):539-47
9252185
Nature. 2007 Oct 18;449(7164):862-6
17943123
Carcinogenesis. 2006 Jun;27(6):1121-5
16699174
Tumour Biol. 2004 May-Jun;25(3):134-40
15361710
Ann N Y Acad Sci. 2008 Sep;1138:162-8
18837897
Cancer Invest. 2009 May;27(4):459-65
19160099
Cancer Res. 2009 Jan 15;69(2):632-9
19147578
J Gastroenterol Hepatol. 2009 Apr;24(4):646-51
19175826
J Exp Med. 2005 Nov 7;202(9):1235-47
16275761
Gut. 2006 Apr;55(4):463-8
16428266
Br J Cancer. 2002 Jun 5;86(11):1817-23
12087472
Science. 2002 Jan 25;295(5555):683-6
11743164
Genes Dev. 2001 Sep 15;15(18):2343-60
11562345
Oncogene. 2003 Oct 9;22(44):6946-53
14534543
Cancer Res. 2008 Jan 15;68(2):379-87
18199531
Int J Cancer. 2008 Feb 15;122(4):823-31
17960618
J Pathol. 2006 Jan;208(2):233-48
16362989
Gastroenterology. 2007 Mar;132(3):1009-23
17383424
Lab Invest. 2008 Feb;88(2):153-60
18059362
Hum Immunol. 2009 Nov;70(11):935-45
19664671
Oncogene. 2003 Jun 19;22(25):3943-51
12813468
Mol Cell. 2002 Oct;10(4):745-55
12419219
Cell. 2000 Jan 7;100(1):57-70
10647931
Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):989-95
16467114
Curr Opin Cell Biol. 2003 Apr;15(2):172-83
12648673
Nat Immunol. 2004 Nov;5(11):1166-74
15489856
Oncogene. 2005 Dec 1;24(54):8051-60
16103878
Nat Genet. 2008 Jun;40(6):741-50
18488029
Gastroenterology. 2004 Nov;127(5):1446-62
15521014
Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9661-6
15980153
Oncogene. 2008 Nov 24;27(55):7047-54
19029944
Mol Microbiol. 2002 Feb;43(4):971-80
11929545
Gastroenterology. 2006 Jan;130(1):188-206; quiz 212-3
16401482
Clin Cancer Res. 2005 Feb 1;11(3):1021-7
15709167
J Biol Chem. 2006 Nov 17;281(46):34888-96
16990273
J Gastroenterol. 2006 May;41(5):401-7
16799880
Cancer Res. 2004 Sep 15;64(18):6410-5
15374948
Appl Immunohistochem Mol Morphol. 2006 Sep;14(3):296-302
16932020
J Pathol. 2005 Jan;205(1):65-73
15586362
Gastroenterology. 2009 Oct;137(4):1367-79.e1-6
19622359
Proteomics. 2004 Oct;4(10):2961-8
15378755
Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14559-64
10588744