Pathobiology of Helicobacter pylori-Induced Gastric Cancer

Gastroenterology

Volumn 150, Issue 1, 2016, Pages 64-78

  Amieva, Manuel ^a   Peek, Richard M ^b,c  

^a STANFORD UNIVERSITY   (United States)

^b VANDERBILT UNIVERSITY   (United States)

^c VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Gastric Cancer; H pylori; Microbiota; Stem Cells

Indexed keywords

CAGA PROTEIN; IRON; ONCOPROTEIN; SODIUM CHLORIDE; TRACE ELEMENT; VIRULENCE FACTOR;

ARTICLE; BACTERIAL CLEARANCE; BACTERIAL COLONIZATION; BACTERIAL GENETICS; BACTERIAL STRAIN; BACTERIAL VIRULENCE; CANCER RESEARCH; CANCER RISK; CANCER STEM CELL; CELL PROLIFERATION; COMMENSAL; DIET; ENVIRONMENTAL FACTOR; EPITHELIUM CELL; GASTRIC MUCOSA; GENETIC VARIABILITY; HELICOBACTER INFECTION; HELICOBACTER PYLORI; HUMAN; IMMUNE SYSTEM; IN VITRO STUDY; IN VIVO STUDY; INTESTINE FLORA; MICROBIAL GENETICS; MUCOSAL IMMUNITY; MULTILOCUS SEQUENCE TYPING; NONHUMAN; NUCLEAR REPROGRAMMING; PRIORITY JOURNAL; PROTEIN EXPRESSION; STEM CELL; STEM CELL NICHE; STOMACH ATROPHY; STOMACH CANCER; STOMACH CARCINOGENESIS; STOMACH EPITHELIUM; STOMACH GLAND; FEMALE; GENETICS; MALE; MICROBIOLOGY; MICROFLORA; PATHOGENICITY; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; PRECANCER; PROGNOSIS; STOMACH MUCOSA; STOMACH TUMOR;

FEMALE; GASTRIC MUCOSA; HELICOBACTER INFECTIONS; HELICOBACTER PYLORI; HUMANS; MALE; MICROBIOTA; PRECANCEROUS CONDITIONS; PROGNOSIS; STOMACH NEOPLASMS;

EID: 84952683442     PISSN: 00165085     EISSN: 15280012     Source Type: Journal    
DOI: 10.1053/j.gastro.2015.09.004     Document Type: Review

References (150)

1. D.M. Hardbower, R.M. Peek Jr., and K.T. Wilson At the bench: Helicobacter pylori, dysregulated host responses, DNA damage, and gastric cancer J Leukoc Biol 96 2014 201 212
2. D.M. Parkin, F. Bray, J. Ferlay, and et al. Global cancer statistics, 2002 CA Cancer J Clin 55 2005 74 108
3. D.B. Polk, and R.M. Peek Jr. Helicobacter pylori: gastric cancer and beyond Nat Rev Cancer 10 2010 403 414
4. B. Linz, F. Balloux, Y. Moodley, and et al. An African origin for the intimate association between humans and Helicobacter pylori Nature 445 2007 915 918
5. Y. Moodley, B. Linz, R.P. Bond, and et al. Age of the association between Helicobacter pylori and man PLoS Pathog 8 2012 e1002693
6. N. Kodaman, A. Pazos, B.G. Schneider, and et al. Human and Helicobacter pylori coevolution shapes the risk of gastric disease Proc Natl Acad Sci U S A 111 2014 1455 1460
7. N. Kodaman, R.S. Sobota, R. Mera, and et al. Disrupted human-pathogen co-evolution: a model for disease Front Genet 5 2014 290
8. C. Holcombe Helicobacter pylori: the African enigma Gut 33 1992 429 431
9. P. Correa, C. Cuello, E. Duque, and et al. Gastric cancer in Colombia. III. Natural history of precursor lesions J Natl Cancer Inst 57 1976 1027 1035
10. T. de Sablet, M.B. Piazuelo, C.L. Shaffer, and et al. Phylogeographic origin of Helicobacter pylori is a determinant of gastric cancer risk Gut 60 2011 1189 1195
11. A.C. de Vries, N.C. van Grieken, C.W. Looman, and et al. Gastric cancer risk in patients with premalignant gastric lesions: a nationwide cohort study in the Netherlands Gastroenterology 134 2008 945 952
12. H. Song, I.G. Ekheden, Z. Zheng, and et al. Incidence of gastric cancer among patients with gastric precancerous lesions: observational cohort study in a low risk Western population BMJ 351 2015 h3867
13. M.R. Amieva, and E.M. El-Omar Host-bacterial interactions in Helicobacter pylori infection Gastroenterology 134 2008 306 323
14. E.M. El-Omar, C.S. Rabkin, M.D. Gammon, and et al. Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms Gastroenterology 124 2003 1193 1201
15. C. Figueiredo, J.C. Machado, P. Pharoah, and et al. Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma J Natl Cancer Inst 94 2002 1680 1687
16. S. Schreiber, M. Konradt, C. Groll, and et al. The spatial orientation of Helicobacter pylori in the gastric mucus Proc Natl Acad Sci U S A 101 2004 5024 5029
17. S. Schreiber, R. Bucker, C. Groll, and et al. Rapid loss of motility of Helicobacter pylori in the gastric lumen in vivo Infect Immun 73 2005 1584 1589
18. E.D. Segal, J. Cha, J. Lo, and et al. Altered states: involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori Proc Natl Acad Sci U S A 96 1999 14559 14564
19. S. Backert, E. Ziska, V. Brinkmann, and et al. Translocation of the Helicobacter pylori CagA protein in gastric epithelial cells by a type IV secretion apparatus Cell Microbiol 2 2000 155 164
20. S. Odenbreit, J. Puls, B. Sedlmaier, and et al. Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion Science 287 2000 1497 1500
21. M. Stein, R. Rappuoli, and A. Covacci Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation Proc Natl Acad Sci U S A 97 2000 1263 1268
22. J. Viala, C. Chaput, I.G. Boneca, and et al. Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island Nat Immunol 5 2004 1166 1174
23. G. Suarez, J. Romero-Gallo, M.B. Piazuelo, and et al. Modification of Helicobacter pylori peptidoglycan enhances NOD1 activation and promotes cancer of the stomach Cancer Res 75 2015 1749 1759
24. M.J. Blaser, G.I. Perez-Perez, H. Kleanthous, and et al. Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach Cancer Res 55 1995 2111 2115
25. S. Censini, C. Lange, Z. Xiang, and et al. cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors Proc Natl Acad Sci U S A 93 1996 14648 14653
26. D. Mueller, N. Tegtmeyer, S. Brandt, and et al. c-Src and c-Abl kinases control hierarchic phosphorylation and function of the CagA effector protein in Western and East Asian Helicobacter pylori strains J Clin Invest 122 2012 1553 1566
27. M. Hatakeyama Helicobacter pylori CagA and gastric cancer: a paradigm for hit-and-run carcinogenesis Cell Host Microbe 15 2014 306 316
28. T.A. Nagy, M.R. Frey, F. Yan, and et al. Helicobacter pylori regulates cellular migration and apoptosis by activation of phosphatidylinositol 3-kinase signaling J Infect Dis 199 2009 641 651
29. M. Suzuki, H. Mimuro, K. Kiga, and et al. Helicobacter pylori CagA phosphorylation-independent function in epithelial proliferation and inflammation Cell Host Microbe 5 2009 23 34
30. S. Keates, A.C. Keates, M. Warny, and et al. Differential activation of mitogen-activated protein kinases in AGS gastric epithelial cells by cag+ and cag- Helicobacter pylori J Immunol 163 1999 5552 5559
31. H. Higashi, R. Tsutsumi, A. Fujita, and et al. Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites Proc Natl Acad Sci U S A 99 2002 14428 14433
32. H. Mimuro, T. Suzuki, J. Tanaka, and et al. Grb2 is a key mediator of Helicobacter pylori CagA protein activities Mol Cell 10 2002 745 755
33. A.T. Franco, D.A. Israel, M.K. Washington, and et al. Activation of B-catenin by carcinogenic Helicobacter pylori Proc Natl Acad Sci U S A 102 2005 10646 10651
34. N. Murata-Kamiya, Y. Kurashima, Y. Teishikata, and et al. Helicobacter pylori CagA interacts with E-cadherin and deregulates the beta-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells Oncogene 26 2007 4617 4626
35. J.T. Neal, T.S. Peterson, M.L. Kent, and et al. H pylori virulence factor CagA increases intestinal cell proliferation by Wnt pathway activation in a transgenic zebrafish model Dis Models Mech 6 2013 802 810
36. L. Buti, E. Spooner, A.G. Van der Veen, and et al. Helicobacter pylori cytotoxin-associated gene A (CagA) subverts the apoptosis-stimulating protein of p53 (ASPP2) tumor suppressor pathway of the host Proc Natl Acad Sci U S A 108 2011 9238 9243
37. J. Wei, J.M. Noto, E. Zaika, and et al. Bacterial CagA protein induces degradation of p53 protein in a p14ARF-dependent manner Gut 64 2015 1040 1048
38. Y.H. Tsang, A. Lamb, J. Romero-Gallo, and et al. Helicobacter pylori CagA targets gastric tumor suppressor RUNX3 for proteasome-mediated degradation Oncogene 29 2010 5643 5650
39. I. Saadat, H. Higashi, C. Obuse, and et al. Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity Nature 447 2007 330 333
40. Z. Zeaiter, D. Cohen, A. Musch, and et al. Analysis of detergent-resistant membranes of Helicobacter pylori infected gastric adenocarcinoma cells reveals a role for MARK2/Par1b in CagA-mediated disruption of cellular polarity Cell Microbiol 10 2008 781 794
41. M.R. Amieva, R. Vogelmann, A. Covacci, and et al. Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA Science 300 2003 1430 1434
42. L.E. Wroblewski, M.B. Piazuelo, R. Chaturvedi, and et al. Helicobacter pylori targets cancer-associated apical-junctional constituents in gastroids and gastric epithelial cells Gut 64 2015 720 730
43. N. Ohnishi, H. Yuasa, S. Tanaka, and et al. Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse Proc Natl Acad Sci U S A 105 2008 1003 1008
44. S. Brandt, T. Kwok, R. Hartig, and et al. NF-kB activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein Proc Natl Acad Sci U S A 102 2005 9300 9305
45. A. Lamb, X.D. Yang, Y.H. Tsang, and et al. Helicobacter pylori CagA activates NF-kappaB by targeting TAK1 for TRAF6-mediated Lys 63 ubiquitination EMBO Rep 10 2009 1242 1249
46. R.J. Gorrell, J. Guan, Y. Xin, and et al. A novel NOD1- and CagA-independent pathway of interleukin-8 induction mediated by the Helicobacter pylori type IV secretion system Cell Microbiol 15 2013 554 570
47. S. Danese, F. Cremonini, A. Armuzzi, and et al. Helicobacter pylori CagA-positive strains affect oxygen free radicals generation by gastric mucosa Scand J Gastroenterol 36 2001 247 250
48. 2 increase AP endonuclease-1/redox factor-1 expression in human gastric epithelial cells Gastroenterology 127 2004 845 858
49. R. Chaturvedi, M. Asim, J. Romero-Gallo, and et al. Spermine oxidase mediates the gastric cancer risk associated with Helicobacter pylori CagA Gastroenterology 141 2011 1696 1708
50. S. Backert, M. Clyne, and N. Tegtmeyer Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori Cell Commun Signal 9 2011 28
51. E. Belogolova, B. Bauer, M. Pompaiah, and et al. Helicobacter pylori outer membrane protein HopQ identified as a novel T4SS-associated virulence factor Cell Microbiol 15 2013 1896 1912
52. T. Kwok, D. Zabler, S. Urman, and et al. Helicobacter exploits integrin for type IV secretion and kinase activation Nature 449 2007 862 866
53. L.F. Jimenez-Soto, S. Kutter, X. Sewald, and et al. Helicobacter pylori type IV secretion apparatus exploits beta1 integrin in a novel RGD-independent manner PLoS Pathog 5 2009 e1000684
54. B. Hoy, M. Lower, C. Weydig, and et al. Helicobacter pylori HtrA is a new secreted virulence factor that cleaves E-cadherin to disrupt intercellular adhesion EMBO Rep 11 2010 798 804
55. R.M. Barrozo, C.L. Cooke, L.M. Hansen, and et al. Functional plasticity in the type IV secretion system of Helicobacter pylori PLoS Pathogens 9 2013 e1003189
56. J.V. Solnick, L.M. Hansen, N.R. Salama, and et al. Modification of Helicobacter pylori outer membrane protein expression during experimental infection of rhesus macaques Proc Natl Acad Sci U S A 101 2004 2106 2111
57. A. Aberg, P. Gideonsson, A. Vallstrom, and et al. A repetitive DNA element regulates expression of the Helicobacter pylori sialic acid binding adhesin by a rheostat-like mechanism PLoS Pathog 10 2014 e1004234
58. F.O. Beltran-Anaya, T.M. Poblete, A. Roman-Roman, and et al. The EPIYA-ABCC motif pattern in CagA of Helicobacter pylori is associated with peptic ulcer and gastric cancer in Mexican population BMC Gastroenterol 14 2014 223
59. X.S. Zhang, N. Tegtmeyer, L. Traube, and et al. A specific A/T polymorphism in Western tyrosine phosphorylation B-motifs regulates Helicobacter pylori CagA epithelial cell interactions PLoS Pathog 11 2015 e1004621
60. C. Pagliaccia, X.M. Wang, F. Tardy, and et al. Structure and interaction of VacA of Helicobacter pylori with a lipid membrane Eur J Biochem 267 2000 104 109
61. M.G. Chambers, T.M. Pyburn, C. Gonzalez-Rivera, and et al. Structural analysis of the oligomeric states of Helicobacter pylori VacA toxin J Mol Biol 425 2013 524 535
62. T.L. Cover, and S.R. Blanke Helicobacter pylori VacA, a paradigm for toxin multifunctionality Nat Rev Microbiol 3 2005 320 332
63. I. Szabo, S. Brutsche, F. Tombola, and et al. Formation of anion-selective channels in the cell plasma membrane by the toxin VacA of Helicobacter pylori is required for its biological activity EMBO J 18 1999 5517 5527
64. E. Papini, B. Satin, N. Norais, and et al. Selective increase of the permeability of polarized epithelial cell monolayers by Helicobacter pylori vacuolating toxin J Clin Invest 102 1998 813 820
65. E. Papini, M. de Bernard, E. Milia, and et al. Cellular vacuoles induced by Helicobacter pylori originate from late endosomal compartments Proc Natl Acad Sci U S A 91 1994 9720 9724
66. D.C. Willhite, T.L. Cover, and S.R. Blanke Cellular vacuolation and mitochondrial cytochrome c release are independent outcomes of Helicobacter pylori vacuolating cytotoxin activity that are each dependent on membrane channel formation J Biol Chem 278 2003 48204 48209
67. I.J. Kim, and S.R. Blanke Remodeling the host environment: modulation of the gastric epithelium by the Helicobacter pylori vacuolating toxin (VacA) Front Cell Infect Microbiol 2 2012 37
68. C. Pagliaccia, M. de Bernard, P. Lupetti, and et al. The m2 form of the Helicobacter pylori cytotoxin has cell type-specific vacuolating activity Proc Natl Acad Sci U S A 95 1998 10212 10217
69. T.L. Cover, U.S. Krishna, D.A. Israel, and et al. Induction of gastric epithelial cell apoptosis by Helicobacter pylori vacuolating cytotoxin Cancer Res 63 2003 951 957
70. B. Gebert, W. Fischer, E. Weiss, and et al. Helicobacter pylori vacuolating cytotoxin inhibits T lymphocyte activation Science 301 2003 1099 1102
71. M. Oertli, M. Noben, D.B. Engler, and et al. Helicobacter pylori gamma-glutamyl transpeptidase and vacuolating cytotoxin promote gastric persistence and immune tolerance Proc Natl Acad Sci U S A 110 2013 3047 3052
72. R.H. Argent, J.L. Hale, E.M. El-Omar, and et al. Differences in Helicobacter pylori CagA tyrosine phosphorylation motif patterns between Western and East Asian strains, and influences on interleukin-8 secretion J Med Microbiol 57 2008 1062 1067
73. A. Oldani, M. Cormont, V. Hofman, and et al. Helicobacter pylori counteracts the apoptotic action of its VacA toxin by injecting the CagA protein into gastric epithelial cells PLoS Pathog 5 2009 e1000603
74. H. Tsugawa, H. Suzuki, H. Saya, and et al. Reactive oxygen species-induced autophagic degradation of Helicobacter pylori CagA is specifically suppressed in cancer stem-like cells Cell Host Microbe 12 2012 764 777
75. L.E. Wroblewski, P.J. Noble, A. Pagliocca, and et al. Stimulation of MMP-7 (matrilysin) by Helicobacter pylori in human gastric epithelial cells: role in epithelial cell migration J Cell Sci 116 2003 3017 3026
76. N. Barker, M. Huch, P. Kujala, and et al. Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro Cell Stem Cell 6 2010 25 36
77. L.E. Wroblewski, L. Shen, S. Ogden, and et al. Helicobacter pylori dysregulation of gastric epithelial tight junctions by urease-mediated myosin II activation Gastroenterology 136 2009 236 246
78. K.W. McCracken, E.M. Cata, C.M. Crawford, and et al. Modelling human development and disease in pluripotent stem-cell-derived gastric organoids Nature 516 2014 400 404
79. N. Bertaux-Skeirik, R. Feng, M.A. Schumacher, and et al. CD44 plays a functional role in Helicobacter pylori-induced epithelial cell proliferation PLoS Pathog 11 2015 e1004663
80. P. Schlaermann, B. Toelle, H. Berger, and et al. A novel human gastric primary cell culture system for modelling Helicobacter pylori infection in vitro Gut 2014 Epub December 24
81. S. Bartfeld, T. Bayram, M. van de Wetering, and et al. In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection Gastroenterology 148 2015 126 136
82. F. Bagnoli, L. Buti, L. Tompkins, and et al. Helicobacter pylori CagA induces a transition from polarized to invasive phenotypes in MDCK cells Proc Natl Acad Sci U S A 102 2005 16339 16344
83. J. Baud, C. Varon, S. Chabas, and et al. Helicobacter pylori initiates a mesenchymal transition through ZEB1 in gastric epithelial cells PLoS One 8 2013 e60315
84. E. Bessede, C. Staedel, L.A. Acuna Amador, and et al. Helicobacter pylori generates cells with cancer stem cell properties via epithelial-mesenchymal transition-like changes Oncogene 33 2014 4123 4131
85. Y. Saito, N. Murata-Kamiya, T. Hirayama, and et al. Conversion of Helicobacter pylori CagA from senescence inducer to oncogenic driver through polarity-dependent regulation of p21 J Exp Med 207 2010 2157 2174
86. Y. Yin, A.M. Grabowska, P.A. Clarke, and et al. Helicobacter pylori potentiates epithelial:mesenchymal transition in gastric cancer: links to soluble HB-EGF, gastrin and matrix metalloproteinase-7 Gut 59 2010 1037 1045
87. T.A. Nagy, L.E. Wroblewski, D. Wang, and et al. β-Catenin and p120 mediate PPARdelta-dependent proliferation induced by Helicobacter pylori in human and rodent epithelia Gastroenterology 141 2011 553 564
88. Y. Fujii, K. Yoshihashi, H. Suzuki, and et al. CDX1 confers intestinal phenotype on gastric epithelial cells via induction of stemness-associated reprogramming factors SALL4 and KLF5 Proc Natl Acad Sci U S A 109 2012 20584 20589
89. J.M. Noto, T. Khizanishvili, R. Chaturvedi, and et al. Helicobacter pylori promotes the expression of Kruppel-like factor 5, a mediator of carcinogenesis, in vitro and in vivo PLoS One 8 2013 e54344
90. C. Panella, E. Ierardi, L. Polimeno, and et al. Proliferative activity of gastric epithelium in progressive stages of Helicobacter pylori infection Dig Dis Sci 41 1996 1132 1138
91. P. Correa Helicobacter pylori and gastric carcinogenesis Am J Surg Pathol 19 1995 S37 S43
92. R.J. Cahill, C. Kilgallen, S. Beattie, and et al. Gastric epithelial cell kinetics in the progression from normal mucosa to gastric carcinoma Gut 38 1996 177 181
93. Q. Li, S.M. Karam, and J.I. Gordon Diphtheria toxin-mediated ablation of parietal cells in the stomach of transgenic mice J Biol Chem 271 1996 3671 3676
94. J.D. Oh, S.M. Karam, and J.I. Gordon Intracellular Helicobacter pylori in gastric epithelial progenitors Proc Natl Acad Sci U S A 102 2005 5186 5191
95. M. Giannakis, S.L. Chen, S.M. Karam, and et al. Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells Proc Natl Acad Sci U S A 105 2008 4358 4363
96. J.D. Oh, H. Kling-Backhed, M. Giannakis, and et al. Interactions between gastric epithelial stem cells and Helicobacter pylori in the setting of chronic atrophic gastritis Curr Opin Microbiol 9 2006 21 27
97. M.R. Howitt, J.Y. Lee, P. Lertsethtakarn, and et al. ChePep controls Helicobacter pylori infection of the gastric glands and chemotaxis in the Epsilonproteobacteria MBio 2011 2
98. M. Sigal, M.E. Rothenberg, C.Y. Logan, and et al. Helicobacter pylori activates and expands Lgr5(+) stem cells through direct colonization of the gastric glands Gastroenterology 148 2015 1392 1404
99. I. Lee, H. Lee, M. Kim, and et al. Ethnic difference of Helicobacter pylori gastritis: Korean and Japanese gastritis is characterized by male- and antrum-predominant acute foveolitis in comparison with American gastritis World J Gastroenterol 11 2005 94 98
100. B.K. Koo, and H. Clevers Stem cells marked by the R-spondin receptor LGR5 Gastroenterology 147 2014 289 302
101. X.T. Qiao, J.W. Ziel, W. McKimpson, and et al. Prospective identification of a multilineage progenitor in murine stomach epithelium Gastroenterology 133 2007 1989 1998
102. K. Arnold, A. Sarkar, M.A. Yram, and et al. Sox2(+) adult stem and progenitor cells are important for tissue regeneration and survival of mice Cell Stem Cell 9 2011 317 329
103. S.M. Karam, and C.P. Leblond Dynamics of epithelial cells in the corpus of the mouse stomach. I. Identification of proliferative cell types and pinpointing of the stem cell Anat Rec 236 1993 259 279
104. J.C. Mills, N. Andersson, C.V. Hong, and et al. Molecular characterization of mouse gastric epithelial progenitor cells Proc Natl Acad Sci U S A 99 2002 14819 14824
105. S.M. Karam, T. Straiton, W.M. Hassan, and et al. Defining epithelial cell progenitors in the human oxyntic mucosa Stem Cells 21 2003 322 336
106. S.S. Khurana, T.E. Riehl, B.D. Moore, and et al. The hyaluronic acid receptor CD44 coordinates normal and metaplastic gastric epithelial progenitor cell proliferation J Biol Chem 288 2013 16085 16097
107. K.T. Nam, H.J. Lee, J.F. Sousa, and et al. Mature chief cells are cryptic progenitors for metaplasia in the stomach Gastroenterology 139 2010 2028 2037
108. D.E. Stange, B.K. Koo, M. Huch, and et al. Differentiated Troy+ chief cells act as reserve stem cells to generate all lineages of the stomach epithelium Cell 155 2013 357 368
109. A.E. Powell, Y. Wang, Y. Li, and et al. The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor Cell 149 2012 146 158
110. Q. Li, Z. Jia, L. Wang, and et al. Disruption of Klf4 in villin-positive gastric progenitor cells promotes formation and progression of tumors of the antrum in mice Gastroenterology 142 2012 531 542
111. T. Uehara, D. Ma, Y. Yao, and et al. H pylori infection is associated with DNA damage of Lgr5-positive epithelial stem cells in the stomach of patients with gastric cancer Dig Dis Sci 58 2013 140 149
112. K. Yamanoi, M. Fukuma, H. Uchida, and et al. Overexpression of leucine-rich repeat-containing G protein-coupled receptor 5 in gastric cancer Pathol Int 63 2013 13 19
113. Z.X. Zheng, Y. Sun, Z.D. Bu, and et al. Intestinal stem cell marker LGR5 expression during gastric carcinogenesis World J Gastroenterol 19 2013 8714 8721
114. H.Q. Xi, A.Z. Cai, X.S. Wu, and et al. Leucine-rich repeat-containing G-protein-coupled receptor 5 is associated with invasion, metastasis, and could be a potential therapeutic target in human gastric cancer Br J Cancer 110 2014 2011 2020
115. J. Houghton, C. Stoicov, S. Nomura, and et al. Gastric cancer originating from bone marrow-derived cells Science 306 2004 1568 1571
116. C. Varon, P. Dubus, F. Mazurier, and et al. Helicobacter pylori infection recruits bone marrow-derived cells that participate in gastric preneoplasia in mice Gastroenterology 142 2012 281 291
117. S. Tan, L.S. Tompkins, and M.R. Amieva Helicobacter pylori usurps cell polarity to turn the cell surface into a replicative niche PLoS Pathog 5 2009 e1000407
118. J. Yamanouchi, T. Azuma, Y. Yakushijin, and et al. Dramatic and prompt efficacy of Helicobacter pylori eradication in the treatment of severe refractory iron deficiency anemia in adults Ann Hematol 93 2014 1779 1780
119. D.M. Queiroz, P.R. Harris, I.R. Sanderson, and et al. Iron status and Helicobacter pylori infection in symptomatic children: an international multi-centered study PLoS One 8 2013 e68833
120. D.M. Queiroz, A.M. Rocha, and J.E. Crabtree Unintended consequences of Helicobacter pylori infection in children in developing countries: iron deficiency, diarrhea, and growth retardation Gut Microbes 4 2013 494 504
121. J.M. Noto, J.A. Gaddy, J.Y. Lee, and et al. Iron deficiency accelerates Helicobacter pylori-induced carcinogenesis in rodents and humans J Clin Invest 123 2013 479 492
122. J.E. Cassat, and E.P. Skaar Iron in infection and immunity Cell Host Microbe 13 2013 509 519
123. Y.H. Choe, Y.J. Oh, N.G. Lee, and et al. Lactoferrin sequestration and its contribution to iron-deficiency anemia in Helicobacter pylori-infected gastric mucosa J Gastroenterol Hepatol 18 2003 980 985
124. J. Velayudhan, N.J. Hughes, A.A. McColm, and et al. Iron acquisition and virulence in Helicobacter pylori: a major role for FeoB, a high-affinity ferrous iron transporter Mol Microbiol 37 2000 274 286
125. M.E. Conrad, and S.G. Schade Ascorbic acid chelates in iron absorption: a role for hydrochloric acid and bile Gastroenterology 55 1968 35 45
126. B. Annibale, G. Capurso, E. Lahner, and et al. Concomitant alterations in intragastric pH and ascorbic acid concentration in patients with Helicobacter pylori gastritis and associated iron deficiency anaemia Gut 52 2003 496 501
127. S.F. Azab, and A.M. Esh Serum hepcidin levels in Helicobacter pylori-infected children with iron-deficiency anemia: a case-control study Ann Hematol 92 2013 1477 1483
128. P. Schwarz, J.A. Kubler, P. Strnad, and et al. Hepcidin is localised in gastric parietal cells, regulates acid secretion and is induced by Helicobacter pylori infection Gut 61 2012 193 201
129. O. Senkovich, S. Ceaser, D.J. McGee, and et al. Unique host iron utilization mechanisms of Helicobacter pylori revealed with iron-deficient chemically defined media Infect Immun 78 2010 1841 1849
130. E. Aihara, C. Closson, A.L. Matthis, and et al. Motility and chemotaxis mediate the preferential colonization of gastric injury sites by Helicobacter pylori PLoS Pathog 10 2014 e1004275
131. S. Tan, J.M. Noto, J. Romero-Gallo, and et al. Helicobacter pylori perturbs iron trafficking in the epithelium to grow on the cell surface PLoS Pathogens 7 2011 e1002050
132. J.M. Noto, J.Y. Lee, J.A. Gaddy, and et al. Regulation of Helicobacter pylori virulence within the context of iron deficiency J Infect Dis 211 2015 1790 1794
133. S.A. Lee, D. Kang, K.N. Shim, and et al. Effect of diet and Helicobacter pylori infection to the risk of early gastric cancer J Epidemiol 13 2003 162 168
134. S. Tsugane Salt, salted food intake, and risk of gastric cancer: epidemiologic evidence Cancer Sci 96 2005 1 6
135. A. Cameron, E. Frirdich, S. Huynh, and et al. Hyperosmotic stress response of Campylobacter jejuni J Bacteriol 194 2012 6116 6130
136. J.T. Loh, V.J. Torres, and T.L. Cover Regulation of Helicobacter pylori cagA expression in response to salt Cancer Res 67 2007 4709 4715
137. J.T. Loh, D.B. Friedman, M.B. Piazuelo, and et al. Analysis of Helicobacter pylori cagA promoter elements required for salt-induced upregulation of CagA expression Infect Immun 80 2012 3094 3106
138. J.T. Loh, C.L. Shaffer, M.B. Piazuelo, and et al. Analysis of cagA in Helicobacter pylori strains from Colombian populations with contrasting gastric cancer risk reveals a biomarker for disease severity Cancer Epidemiol Biomarks Prev 20 2011 2237 2249
139. J.G. Fox, C.A. Dangler, N.S. Taylor, and et al. High-salt diet induces gastric epithelial hyperplasia and parietal cell loss, and enhances Helicobacter pylori colonization in C57BL/6 mice Cancer Res 59 1999 4823 4828
140. I.L. Bergin, B.J. Sheppard, and J.G. Fox Helicobacter pylori infection and high dietary salt independently induce atrophic gastritis and intestinal metaplasia in commercially available outbred Mongolian gerbils Dig Dis Sci 48 2003 475 485
141. K. Nozaki, N. Shimizu, K. Inada, and et al. Synergistic promoting effects of Helicobacter pylori infection and high-salt diet on gastric carcinogenesis in Mongolian gerbils Jpn J Can Res 93 2002 1083 1089
142. J.A. Gaddy, J.N. Radin, J.T. Loh, and et al. High dietary salt intake exacerbates Helicobacter pylori-induced gastric carcinogenesis Infect Immun 81 2013 2258 2267
143. H. Tilg Diet and intestinal immunity N Engl J Med 366 2012 181 183
144. T.A. Gonda, Y.I. Kim, M.C. Salas, and et al. Folic acid increases global DNA methylation and reduces inflammation to prevent Helicobacter-associated gastric cancer in mice Gastroenterology 142 2012 824 833
145. M.T. Abreu, and R.M. Peek Jr. Gastrointestinal malignancy and the microbiome Gastroenterology 146 2014 1534 1546 e3
146. J.L. Ma, L. Zhang, L.M. Brown, and et al. Fifteen-year effects of Helicobacter pylori, garlic, and vitamin treatments on gastric cancer incidence and mortality J Natl Can Inst 104 2012 488 492
147. J.L. Lofgren, M.T. Whary, Z. Ge, and et al. Lack of commensal flora in Helicobacter pylori-infected INS-GAS mice reduces gastritis and delays intraepithelial neoplasia Gastroenterology 140 2011 210 220
148. K. Lertpiriyapong, M.T. Whary, S. Muthupalani, and et al. Gastric colonisation with a restricted commensal microbiota replicates the promotion of neoplastic lesions by diverse intestinal microbiota in the Helicobacter pylori INS-GAS mouse model of gastric carcinogenesis Gut 63 2013 54 63
149. L.B. Lemke, Z. Ge, M.T. Whary, and et al. Concurrent Helicobacter bilis infection in C57BL/6 mice attenuates proinflammatory H pylori-induced gastric pathology Infect Immun 77 2009 2147 2158
150. Z. Ge, Y. Feng, S. Muthupalani, and et al. Coinfection with Enterohepatic Helicobacter species can ameliorate or promote Helicobacter pylori-induced gastric pathology in C57BL/6 mice Infect Immun 79 2011 3861 3871