Microbes-induced EMT at the crossroad of inflammation and cancer

Gut Microbes

Volumn 3, Issue 3, 2012, Pages 176-185

  Hofman, Paul ^a,c   Vouret Craviari, Valérie ^a,b  

^a UNIVERSITY OF NICE SOPHIA ANTIPOLIS   (France)

^b UNIVERSITÉ CÔTE D'AZUR   (France)

^c PASTEUR HOSPITAL   (France)

Author keywords

E cadherin; E. coli; H. pylori; Pathogens; Tumor

Indexed keywords

FLAGELLIN; HELIX LOOP HELIX PROTEIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MICRORNA; MITOGEN ACTIVATED PROTEIN KINASE; MURAMYL DIPEPTIDE; PATTERN RECOGNITION RECEPTOR; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; SMAD PROTEIN; STAT PROTEIN; TOLL LIKE RECEPTOR; TRANSCRIPTION FACTOR; UVOMORULIN; VIMENTIN; ZINC FINGER PROTEIN;

BACTERIAL COLONIZATION; BACTERIAL INFECTION; BACTERIAL VIRULENCE; CANCER CELL; CHRONIC INFLAMMATION; DISEASE PREDISPOSITION; ENZYME ACTIVATION; EPITHELIAL MESENCHYMAL TRANSITION; EPSTEIN BARR VIRUS; ESCHERICHIA COLI; FIBRIN FORMATION; HELICOBACTER PYLORI; HEPATITIS B VIRUS; HEPATITIS C VIRUS; HUMAN; INFLAMMATION; INNATE IMMUNITY; METASTASIS; NEOPLASM; NONHUMAN; REVIEW; SIGNAL TRANSDUCTION; VIRUS INFECTION; ANIMAL; BACTERIUM; BIOLOGICAL MODEL; EPITHELIUM; GENE EXPRESSION REGULATION; MESODERM; METAPLASIA; MICROBIOLOGY; PATHOGENICITY; PATHOLOGY;

BACTERIA (MICROORGANISMS); HELICOBACTER PYLORI;

ANIMALS; BACTERIA; EPITHELIUM; GENE EXPRESSION REGULATION; HUMANS; INFLAMMATION; MESODERM; METAPLASIA; MODELS, BIOLOGICAL; NEOPLASMS;

EID: 84930477581     PISSN: 19490976     EISSN: 19490984     Source Type: Journal    
DOI: 10.4161/gmic.20288     Document Type: Review

References (105)

1. Farquhar MG, Palade GE. Junctional complexes in various epithelia. J Cell Biol 1963; 17:375-412. PMID:13944428; http://dx.doi.org/10.1083/jcb.17.2.375.
2. Grününert S, Jechlinger M, Beug H. Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nat Rev Mol Cell Biol 2003; 4:657-665. PMID:12923528; http://dx.doi.org/10.1038/nrm1175.
3. Nieto MA. The ins and outs of the epithelial to mesenchymal transition in health and disease. Annu Rev Cell Dev Biol 2011; 27:347-376. PMID:21740232; http://dx.doi.org/10.1146/annurev-cellbio-092910-154036.
4. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2002; 2:442-454. PMID:12189386; http://dx.doi.org/10.1038/nrc822.
5. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell 2009; 139:871-890. PMID:19945376;http://dx.doi.org/10.1016/j.cell.2009.11.007.
6. Ilina O, Friedl P. Mechanisms of collective cell migration at a glance. J Cell Sci 2009; 122:3203-3208. PMID:19726629; http://dx.doi.org/10.1242/jcs.036525.
7. Champsi J, Young LS, Bermudez LE. Production of TNFalpha, IL-6 and TGFbeta, and expression of receptors for TNFalpha and IL-6, during murine Mycobacterium avium infection. Immunology 1995; 84:549-554. PMID:7790028.
8. Reed SG. TGFbeta in infections and infectious diseases. Microbes Infect 1999; 1:1313-1325. PMID:10611760;http://dx.doi.org/10.1016/S1286-4579(99)00252-X.
9. Silva JS, Twardzik DR, Reed SG. Regulation of Trypanosoma cruzi infections in vitro and in vivo by transforming growth factorbeta (TGFbeta). J Exp Med 1991; 174:539-545. PMID:1908509; http://dx.doi.org/10.1084/jem.174.3.539.
10. Massaguün J. TGFbeta signal transduction. Annu Rev Biochem 1998; 67:753-791. PMID:9759503; http://dx.doi.org/10.1146/annurev.biochem.67.1.753.
11. Wu JW, Hu M, Chai J, Seoane J, Huse M, Li C, et al. Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGFbeta signaling. Mol Cell 2001; 8:1277-1289. PMID:11779503; http://dx.doi.org/10.1016/S1097-2765(01)00421-X.
12. Said NA, Williams ED. Growth factors in induction of epithelial-mesenchymal transition and metastasis. Cells Tissues Organs 2011; 193:85-97. PMID:21051862;http://dx.doi.org/10.1159/000320360.
13. Twigg SR, Wilkie AO. Characterisation of the human snail (SNAI1) gene and exclusion as a major disease gene in craniosynostosis. Hum Genet 1999; 105:320-326. PMID:10543399; http://dx.doi.org/10.1007/s004390051108.
14. Cohen ME, Yin M, Paznekas WA, Schertzer M, Wood S, Jabs EW. Human SLUG gene organization, expression and chromosome map location on 8q. Genomics 1998; 51:468-471. PMID:9721220; http://dx.doi.org/10.1006/geno.1998.5367.
15. Verschueren K, Remacle JE, Collart C, Kraft H, Baker BS, Tylzanowski P, et al. SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5'-CAC CT sequences in candidate target genes. J Biol Chem 1999; 274:20489-20498. PMID:10400677; http://dx.doi.org/10.1074/jbc.274.29.20489.
16. Wang SM, Coljee VW, Pignolo RJ, Rotenberg MO, Cristofalo VJ, Sierra F. Cloning of the human twist gene: its expression is retained in adult mesodermally-derived tissues. Gene 1997; 187:83-92. PMID:9073070; http://dx.doi.org/10.1016/S0378-1119(96)00727-5.
17. Peinado H, Olmeda D, Cano A. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 2007; 7:415-428. PMID:17508028; http://dx.doi.org/10.1038/nrc2131.
18. Lander R, Nordin K, LaBonne C. The F-box protein Ppa is a common regulator of core EMT factors Twist, Snail, Slug and Sip1. J Cell Biol 2011; 194:17-25. PMID:21727196; http://dx.doi.org/10.1083/jcb.201012085.
19. Dansen TB, Burgering BM. Unravelling the tumorsuppressive functions of FOXO proteins. Trends Cell Biol 2008; 18:421-429. PMID:18715783; http://dx.doi.org/10.1016/j.tcb.2008.07.004.
20. Shiota M, Song Y, Yokomizo A, Kiyoshima K, Tada Y, Uchino H, et al. Foxo3a suppression of urothelial cancer invasiveness through Twist1, Y-box-binding protein 1 and E-cadherin regulation. Clin Cancer Res 2010; 16:5654-5663. PMID:21138866; http://dx.doi.org/10.1158/1078-0432.CCR-10-0376.
21. Snoeks L, Weber CR, Turner JR, Bhattacharyya M, Wasland K, Savkovic SD. Tumor suppressor Foxo3a is involved in the regulation of lipopolysaccharideinduced interleukin-8 in intestinal HT-29 cells. Infect Immun 2008; 76:4677-4685. PMID:18678662; http://dx.doi.org/10.1128/IAI.00227-08.
22. Israël A. The IKK complex, a central regulator of NFkappaB activation. Cold Spring Harb Perspect Biol 2010; 2:158. PMID:20300203; http://dx.doi.org/10.1101/cshperspect.a000158.
23. Min C, Eddy SF, Sherr DH, Sonenshein GE. NFkappaB and epithelial to mesenchymal transition of cancer. J Cell Biochem 2008; 104:733-744. PMID:18253935;http://dx.doi.org/10.1002/jcb.21695.
24. Li Q, Verma IM. NFkappaB regulation in the immune system. Nat Rev Immunol 2002; 2:725-734. PMID:12360211; http://dx.doi.org/10.1038/nri910.
25. Katoh M, Katoh M. Integrative genomic analyses of ZEB2: Transcriptional regulation of ZEB2 based on SMADs, ETS1, HIF1alpha, POU/OCT and NFkappaB. Int J Oncol 2009; 34:1737-1742. PMID:19424592; http://dx.doi.org/10.3892/ijo_00000304.
26. Šošiæ D, Richardson JA, Yu K, Ornitz DM, Olson EN. Twist regulates cytokine gene expression through a negative feedback loop that represses NFkappaB activity. Cell 2003; 112:169-180. PMID:12553906; http://dx.doi.org/10.1016/S0092-8674(03)00002-3.
27. Pantuck AJ, An J, Liu H, Rettig MB. NFkappaBdependent plasticity of the epithelial to mesenchymal transition induced by Von Hippel-Lindau inactivation in renal cell carcinomas. Cancer Res 2010; 70:752-761. PMID:20068166; http://dx.doi.org/10.1158/0008-5472.CAN-09-2211.
28. Lilienbaum A, Duc Dodon M, Alexandre C, Gazzolo L, Paulin D. Effect of human T-cell leukemia virus type I tax protein on activation of the human vimentin gene. J Virol 1990; 64:256-263. PMID:2293664.
29. Chua HL, Bhat-Nakshatri P, Clare SE, Morimiya A, Badve S, Nakshatri H. NFkappaB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells: potential involvement of ZEB-1 and ZEB-2. Oncogene 2007; 26:711-724. PMID:16862183; http://dx.doi.org/10.1038/sj.onc.1209808.
30. Himelstein BP, Lee EJ, Sato H, Seiki M, Muschel RJ. Transcriptional activation of the matrix metalloproteinase- 9 gene in an H-ras and v-myc transformed rat embryo cell line. Oncogene 1997; 14:1995-1998. PMID:9150367; http://dx.doi.org/10.1038/sj.onc.1201012.
31. Yoshizaki T, Sato H, Furukawa M. Recent advances in the regulation of matrix metalloproteinase 2 activation: from basic research to clinical implication (Review). Oncol Rep 2002; 9:607-611. PMID:11956636.
32. Junttila MR, Li SP, Westermarck J. Phosphatasemediated crosstalk between MAPK signaling pathways in the regulation of cell survival. FASEB J 2008; 22:954-965. PMID:18039929; http://dx.doi.org/10.1096/fj.06-7859rev.
33. Keshet Y, Seger R. The MAP kinase signaling cascades: a system of hundreds of components regulates a diverse array of physiological functions. Methods Mol Biol 2010; 661:3-38. PMID:20811974; http://dx.doi.org/10.1007/978-1-60761-795-2_1.
34. Zohn IE, Li Y, Skolnik EY, Anderson KV, Han J, Niswander L. p38 and a p38-interacting protein are critical for downregulation of E-cadherin during mouse gastrulation. Cell 2006; 125:957-969. PMID:16751104;http://dx.doi.org/10.1016/j.cell.2006.03.048.
35. Grund EM, Kagan D, Tran CA, Zeitvogel A, Starzinski-Powitz A, Nataraja S, et al. Tumor necrosis factoralpha regulates inflammatory and mesenchymal responses via mitogen-activated protein kinase kinase, p38 and nuclear factorkappaB in human endometriotic epithelial cells. Mol Pharmacol 2008; 73:1394-1404. PMID:18252806; http://dx.doi.org/10.1124/mol.107.042176.
36. Borthwick LA, Gardner A, De Soyza A, Mann DA, Fisher AJ. Transforming Growth Factor-beta1 (TGFbeta1) Driven Epithelial to Mesenchymal Transition (EMT) is Accentuated by Tumour Necrosis Factor alpha (TNFalpha) via Crosstalk Between the SMAD and NFkappaB Pathways. Cancer Microenviron 2011.
37. Santibañez JF. JNK mediates TGF-beta1-induced epithelial mesenchymal transdifferentiation of mouse transformed keratinocytes. FEBS Lett 2006; 580:5385-5391. PMID:16989819; http://dx.doi.org/10.1016/j.febslet.2006.09.003.
38. Liu Q, Mao H, Nie J, Chen W, Yang Q, Dong X, et al. Transforming growth factor beta1 induces epithelialmesenchymal transition by activating the JNK-Smad3 pathway in rat peritoneal mesothelial cells. Perit Dial Int 2008; 28:88-95. PMID:18552272.
39. Grille SJ, Bellacosa A, Upson J, Klein-Szanto AJ, van Roy F, Lee-Kwon W, et al. The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res 2003; 63:2172-2178. PMID:12727836.
40. Bakin AV, Tomlinson AK, Bhowmick NA, Moses HL, Arteaga CL. Phosphatidylinositol-3-kinase function is required for transforming growth factor beta-mediated epithelial to mesenchymal transition and cell migration. J Biol Chem 2000; 275:36803-36810. PMID:10969078;http://dx.doi.org/10.1074/jbc.M005912200.
41. Toossi Z, Young TG, Averill LE, Hamilton BD, Shiratsuchi H, Ellner JJ. Induction of transforming growth factorbeta1 by purified protein derivative of Mycobacterium tuberculosis. Infect Immun 1995; 63:224-228. PMID:7806361.
42. Reich NC, Liu L. Tracking STAT nuclear traffic. Nat Rev Immunol 2006; 6:602-612. PMID:16868551;http://dx.doi.org/10.1038/nri1885.
43. Takeda K, Noguchi K, Shi W, Tanaka T, Matsumoto M, Yoshida N, et al. Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc Natl Acad Sci USA 1997; 94:3801-3804. PMID:9108058;http://dx.doi.org/10.1073/pnas.94.8.3801.
44. Huang C, Yang G, Jiang T, Zhu G, Li H, Qiu Z. The effects and mechanisms of blockage of STAT3 signaling pathway on IL-6 inducing EMT in human pancreatic cancer cells in vitro. Neoplasma 2011; 58:396-405. PMID:21744993; http://dx.doi.org/10.4149/neo_2011_05_396.
45. Haase VH. Oxygen regulates epithelial-to-mesenchymal transition: insights into molecular mechanisms and relevance to disease. Kidney Int 2009; 76:492-499. PMID:19536078; http://dx.doi.org/10.1038/ki.2009.222.
46. Jiang J, Tang YL, Liang XH. EMT: a new vision of hypoxia promoting cancer progression. Cancer Biol Ther 2011; 11:714-723. PMID:21389772; http://dx.doi.org/10.4161/cbt.11.8.15274.
47. Blouin CC, Pagün EL, Soucy GM, Richard DE. Hypoxic gene activation by lipopolysaccharide in macrophages: implication of hypoxia-inducible factor 1alpha. Blood 2004; 103:1124-1130. PMID:14525767; http://dx.doi.org/10.1182/blood-2003-07-2427.
48. Cane G, Eń A, Marchetti S, BuscünR, Pouysségur J, Berra E, et al. HIF-1alpha mediates the induction of IL-8 and VEGF expression on infection with Afa/Dr diffusely adhering E. coli and promotes EMTlike behaviour. Cell Microbiol 2010; 12:640-653. PMID:20039880; http://dx.doi.org/10.1111/j.1462-5822.2009.01422.x.
49. Jung YJ, Isaacs JS, Lee S, Trepel J, Neckers L. IL-1beta-mediated upregulation of HIF-1alpha via an NFkappaB/COX-2 pathway identifies HIF-1 as a critical link between inflammation and oncogenesis. FASEB J 2003; 17:2115-2117. PMID:12958148.
50. Peyssonnaux C, Boutin AT, Zinkernagel AS, Datta V, Nizet V, Johnson RS. Critical role of HIF-1alpha in keratinocyte defense against bacterial infection. J Invest Dermatol 2008; 128:1964-1968. PMID:18323789; http://dx.doi.org/10.1038/jid.2008.27.
51. Zhou J, Schmid T, Brüne B. Tumor necrosis factoralpha causes accumulation of a ubiquitinated form of hypoxia inducible factor-1alpha through a nuclear factorkappaB-dependent pathway. Mol Biol Cell 2003; 14:2216-2225. PMID:12808024; http://dx.doi.org/10.1091/mbc.E02-09-0598.
52. Bracken CP, Gregory PA, Kolesnikoff N, Bert AG, Wang J, Shannon MF, et al. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res 2008; 68:7846-7854. PMID:18829540;http://dx.doi.org/10.1158/0008-5472.CAN-08-1942.
53. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol 2008; 10:593-601. PMID:18376396; http://dx.doi.org/10.1038/ncb1722.
54. Korpal M, Lee ES, Hu G, Kang Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem 2008; 283:14910-14914. PMID:18411277; http://dx.doi.org/10.1074/jbc.C800074200.
55. Park SM, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev 2008; 22:894-907. PMID:18381893; http://dx.doi.org/10.1101/gad.1640608.
56. Janeway CA Jr. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol 1989; 54:1-13. PMID:2700931;http://dx.doi.org/10.1101/SQB.1989.054.01.003.
57. Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatory gene cassette späzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 1996; 86:973-983. PMID:8808632; http://dx.doi.org/10.1016/S0092-8674(00)80172-5.
58. Medzhitov R, Preston-Hurlburt P, Janeway CA Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 1997; 388:394-397. PMID:9237759; http://dx.doi.org/10.1038/41131.
59. Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 1998; 282:2085-2088. PMID:9851930; http://dx.doi.org/10.1126/science.282.5396.2085.
60. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 2010; 11:373-384. PMID:20404851;http://dx.doi.org/10.1038/ni.1863.
61. Athman R, Philpott D. Innate immunity via Toll-like receptors and Nod proteins. Curr Opin Microbiol 2004; 7:25-32. PMID:15036136; http://dx.doi.org/10.1016/j.mib.2003.12.013.
62. Bouchon A, Dietrich J, Colonna M. Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. J Immunol 2000; 164:4991-4995. PMID:10799849.
63. Crocker PR. Siglecs in innate immunity. Curr Opin Pharmacol 2005; 5:431-437. PMID:15955740; http://dx.doi.org/10.1016/j.coph.2005.03.003.
64. Klesney-Tait J, Turnbull IR, Colonna M. The TREM receptor family and signal integration. Nat Immunol 2006; 7:1266-1273. PMID:17110943; http://dx.doi.org/10.1038/ni1411.
65. Robinson MJ, Sancho D, Slack EC, Leibund Gut-Landmann S, Reise Sousa C. Myeloid C-type lectins in innate immunity. Nat Immunol 2006; 7:1258-1265. PMID:17110942; http://dx.doi.org/10.1038/ni1417.
66. Kobayashi K, Inohara N, Hernandez LD, Eń JE, Naúñez G, Janeway CA, et al. RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature 2002; 416:194-199. PMID:11894098; http://dx.doi.org/10.1038/416194a.
67. Inohara N, Koseki T, Lin J, del Peso L, Lucas PC, Chen FF, et al. An induced proximity model for NFkappaB activation in the Nod1/RICK and RIP signaling pathways. J Biol Chem 2000; 275:27823-27831. PMID:10880512.
68. Hazeki K, Nigorikawa K, Hazeki O. Role of phosphoinositide-3-kinase in innate immunity. Biol Pharm Bull 2007; 30:1617-1623. PMID:17827709; http://dx.doi.org/10.1248/bpb.30.1617.
69. Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 2006; 124:837-848. PMID:16497592;http://dx.doi.org/10.1016/j.cell.2006.02.017.
70. Inagaki H, Suzuki T, Nomoto K, Yoshikai Y. Increased susceptibility to primary infection with Listeria monocytogenes in germfree mice may be due to lack of accumulation of L-selectin+ CD44+ T cells in sites of inflammation. Infect Immun 1996; 64:3280-3287. PMID:8757865.
71. Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 2009; 9:313-323. PMID:19343057;http://dx.doi.org/10.1038/nri2515.
72. Zhao L, Yang R, Cheng L, Wang M, Jiang Y, Wang S. LPS-induced epithelial-mesenchymal transition of intrahepatic biliary epithelial cells. J Surg Res 2011; 171:819-825. PMID:20691985; http://dx.doi.org/10.1016/j.jss.2010.04.059.
73. Honko AN, Mizel SB. Effects of flagellin on innate and adaptive immunity. Immunol Res 2005; 33:83-101. PMID:16120974; http://dx.doi.org/10.1385/IR:33:1:083.
74. Yang JJ, Wang DD, Sun TY. Flagellin of Pseudomonas aeruginosa induces transforming growth factorbeta1 expression in normal bronchial epithelial cells through mitogen activated protein kinase cascades. Chin Med J (Engl) 2011; 124:599-605. PMID:21362288.
75. Franchi L, Park JH, Shaw MH, Marina-Garcia N, Chen G, Kim YG, et al. Intracellular NOD-like receptors in innate immunity, infection and disease. Cell Microbiol 2008; 10:1-8. PMID:17944960.
76. Smith MF Jr, Mitchell A, Li G, Ding S, Fitzmaurice AM, Ryan K, et al. Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NFkappaB activation and chemokine expression by epithelial cells. J Biol Chem 2003; 278:32552-32560. PMID:12807870; http://dx.doi.org/10.1074/jbc.M305536200.
77. Papini E, Satin B, Norais N, de Bernard M, Telford JL, Rappuoli R, et al. Selective increase of the permeabilityof polarized epithelial cell monolayers by Helicobacter pylori vacuolating toxin. J Clin Invest 1998; 102:813-820. PMID:9710450; http://dx.doi.org/10.1172/JCI2764.
78. Amieva MR, Vogelmann R, Covacci A, Tompkins LS, Nelson WJ, Falkow S. Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science 2003; 300:1430-1434. PMID:12775840; http://dx.doi.org/10.1126/science.1081919.
79. Murata-Kamiya N, Kurashima Y, Teishikata Y, Yamahashi Y, Saito Y, Higashi H, et al. Helicobacter pylori CagA interacts with E-cadherin and deregulates the beta-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells. Oncogene 2007; 26:4617-4626. PMID:17237808; http://dx.doi.org/10.1038/sj.onc.1210251.
80. Yin Y, Grabowska AM, Clarke PA, Whelband E, Robinson K, Argent RH, et al. Helicobacter pylori potentiates epithelial:mesenchymal transition in gastric cancer: links to soluble HB-EGF, gastrin and matrix metalloproteinase-7. Gut 2010; 59:1037-1045. PMID:20584780; http://dx.doi.org/10.1136/gut.2009.199794.
81. Brandt S, Kwok T, Hartig R, König W, Backert S. NFkappaB activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein. Proc Natl Acad Sci USA 2005; 102:9300-9305. PMID:15972330; http://dx.doi.org/10.1073/pnas.0409873102.
82. Kaper JB, Nataro JP, Mobley HL. Pathogenic Escherichia coli. Nat Rev Microbiol 2004; 2:123-140. PMID:15040260; http://dx.doi.org/10.1038/nrmicro818.
83. Servin AL. Pathogenesis of Afa/Dr diffusely adhering Escherichia coli. Clin Microbiol Rev 2005; 18:264-292. PMID:15831825; http://dx.doi.org/10.1128/CMR.18.2.264-92.2005.
84. Bétis F, Brest P, Hofman V, Guignot J, Bernet-Camard MF, Rossi B, et al. The Afa/Dr adhesins of diffusely adhering Escherichia coli stimulate interleukin-8 secretion, activate mitogen-activated protein kinases and promote polymorphonuclear transepithelial migration in T84 polarized epithelial cells. Infect Immun 2003; 71:1068-1074. PMID:12595416; http://dx.doi.org/10.1128/IAI.71.3.1068-74.2003.
85. Bétis F, Brest P, Hofman V, Guignot J, Kansau I, Rossi B, et al. Afa/Dr diffusely adhering Escherichia coli infection in T84 cell monolayers induces increased neutrophil transepithelial migration, which in turn promotes cytokine-dependent upregulation of decay-accelerating factor (CD55), the receptor for Afa/Dr adhesins. Infect Immun 2003; 71:1774-1783. PMID:12654791; http://dx.doi.org/10.1128/IAI.71.4.1774-83.2003.
86. Cane G, Moal VL, Pagè G, Servin AL, Hofman P, Vouret-Craviari V. Upregulation of intestinal vascular endothelial growth factor by Afa/Dr diffusely adhering Escherichia coli. PLoS One 2007; 2:1359. PMID:18159242; http://dx.doi.org/10.1371/journal.pone.0001359.
87. Rathinam VA, Fitzgerald KA. Innate immune sensing of DNA viruses. Virology 2011; 411:153-162. PMID:21334037; http://dx.doi.org/10.1016/j.virol.2011.02.003.
88. Martin HJ, Lee JM, Walls D, Hayward SD. Manipulation of the toll-like receptor 7 signaling pathway by Epstein-Barr virus. J Virol 2007; 81:9748-9758. PMID:17609264; http://dx.doi.org/10.1128/JVI.01122-07.
89. Gaudreault E, Fiola S, Olivier M, Gosselin J. Epstein-Barr virus induces MCP-1 secretion by humanmonocytes via TLR2. J Virol 2007; 81:8016-8024. PMID:17522215; http://dx.doi.org/10.1128/JVI.00403-07.
90. Chen MR. Epstein-barr virus, the immune system and associated diseases. Front Microbiol 2011; 2:5. PMID:21687403; http://dx.doi.org/10.3389/fmicb.2011.00005.
91. Gires O, Zimber-Strobl U, Gonnella R, Ueffing M, Marschall G, Zeidler R, et al. Latent membrane protein 1 of Epstein-Barr virus mimics a constitutively active receptor molecule. EMBO J 1997; 16:6131-6140. PMID:9359753; http://dx.doi.org/10.1093/emboj/16.20.6131.
92. Caldwell RG, Wilson JB, Anderson SJ, Longnecker R. Epstein-Barr virus LMP2A drives B cell development and survival in the absence of normal B cell receptor signals. Immunity 1998; 9:405-411. PMID:9768760;http://dx.doi.org/10.1016/S1074-7613(00)80623-8.
93. Horikawa T, Yang J, Kondo S, Yoshizaki T, Joab I, Furukawa M, et al. Twist and epithelial-mesenchymal transition are induced by the EBV oncoprotein latent membrane protein 1 and are associated with metastatic nasopharyngeal carcinoma. Cancer Res 2007; 67:1970-1978. PMID:17332324; http://dx.doi.org/10.1158/0008-5472.CAN-06-3933.
94. Horikawa T, Yoshizaki T, Kondo S, Furukawa M, Kaizaki Y, Pagano JS. Epstein-Barr Virus latent membrane protein 1 induces Snail and epithelial-mesenchymal transition in metastatic nasopharyngeal carcinoma. Br J Cancer 2011; 104:1160-1167. PMID:21386845;http://dx.doi.org/10.1038/bjc.2011.38.
95. Malizia AP, Lacey N, Walls D, Egan JJ, Doran PP. CUX1/Wnt signaling regulates epithelial mesenchymal transition in EBV infected epithelial cells. Exp Cell Res 2009; 315:1819-1831. PMID:19361498; http://dx.doi.org/10.1016/j.yexcr.2009.04.001.
96. Sides MD, Klingsberg RC, Shan B, Gordon KA, Nguyen HT, Lin Z, et al. The Epstein-Barr virus latent membrane protein 1 and transforming growth factorβ1 synergistically induce epithelial-mesenchymal transition in lung epithelial cells. Am J Respir Cell Mol Biol 2011; 44:852-862. PMID:20693406; http://dx.doi.org/10.1165/rcmb.2009-0232OC.
97. Shinozaki A, Sakatani T, Ushiku T, Hino R, Isogai M, Ishikawa S, et al. Downregulation of microRNA-200 in EBV-associated gastric carcinoma. Cancer Res 2010; 70:4719-4727. PMID:20484038; http://dx.doi.org/10.1158/0008-5472.CAN-09-4620.
98. Yang SZ, Zhang LD, Zhang Y, Xiong Y, Zhang YJ, Li HL, et al. HBx protein induces EMT through c-Src activation in SMMC-7721 hepatoma cell line. Biochem Biophys Res Commun 2009; 382:555-560. PMID:19302982; http://dx.doi.org/10.1016/j.bbrc.2009.03.079.
99. Zhu N, Khoshnan A, Schneider R, Matsumoto M, Dennert G, Ware C, et al. Hepatitis C virus core protein binds to the cytoplasmic domain of tumor necrosis factor (TNF) receptor 1 and enhances TNF-induced apoptosis. J Virol 1998; 72:3691-3697. PMID:9557650.
100. Delhem N, Sabile A, Gajardo R, Podevin P, Abadie A, Blaton MA, et al. Activation of the interferoninducible protein kinase PKR by hepatocellular carcinoma derived-hepatitis C virus core protein. Oncogene 2001; 20:5836-5845. PMID:11593389; http://dx.doi.org/10.1038/sj.onc.1204744.
101. Lai MM, Ware CF. Hepatitis C virus core protein: possible roles in viral pathogenesis. Curr Top Microbiol Immunol 2000; 242:117-134. PMID:10592658; http://dx.doi.org/10.1007/978-3-642-59605-6_6.
102. Pavio N, Battaglia S, Boucreux D, Arnulf B, Sobesky R, Hermine O, et al. Hepatitis C virus core variants isolated from liver tumor but not from adjacent non-tumor tissue interact with Smad3 and inhibit the TGFbeta pathway. Oncogene 2005; 24:6119-6132. PMID:16007207; http://dx.doi.org/10.1038/sj.onc.1208749.
103. Battaglia S, Benzoubir N, Nobilet S, Charneau P, Samuel D, Zignego AL, et al. Liver cancer-derived hepatitis C virus core proteins shift TGFbeta responses from tumor suppression to epithelial-mesenchymal transition. PLoS One 2009; 4:4355. PMID:19190755;http://dx.doi.org/10.1371/journal.pone.0004355.
104. Li T, Li D, Cheng L, Wu H, Gao Z, Liu Z, et al. Epithelial-mesenchymal transition induced by hepatitis C virus core protein in cholangiocarcinoma. Ann Surg Oncol 2010; 17:1937-1944. PMID:20162464; http://dx.doi.org/10.1245/s10434-010-0925-3.
105. Hofman PM. Pathobiology of the neutrophil-intestinal epithelial cell interaction: role in carcinogenesis. World J Gastroenterol 2010; 16:5790-5800. PMID:21154999;http://dx.doi.org/10.3748/wjg.v16.i46.5790.