Abstract
Helicobacter pylori is the first bacterium formally recognized to play a causative role in human malignancies, gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Evidence accumulates that H. pylori cagA-positive strains play a crucial role in the neoplastic transformation of mammalian cells. The cagA-encoded CagA protein is delivered into the host cells via bacterial type IV secretion, where it interacts with and thereby aberrantly activates pro-oncogenic phosphatase SHP2. The CagA-SHP2 interaction requires tyrosine phosphorylation of CagA at the Glu-Pro-Ile-Tyr-Ala (EPIYA) motif. The incidences of gastric cancer in East Asian countries such as Japan, China, and Korea are among the highest worldwide. A vast majority of H. pylori circulating in East Asia produce a CagA variant termed East Asian CagA, which possesses the SHP2-binding EPIYA motif (EPIYA-D) that is substantially diverged in sequence from the SHP2-binding EPIYA motif (EPIYA-C) of CagA isolated in the rest of the world (Western CagA). Tyrosine-phosphorylated EPIYA-D interacts with SHP2 approximately two orders of magnitude stronger than tyrosine-phosphorylated EPIYA-C does. The strong SHP2 binding of East Asian CagA is achieved by a cryptic interaction between the phenylalanine residue located at the +5 position from the phospho-tyrosine in EPIYA-D and a small hollow on the N-SH2 phosphopeptide-binding floor, the latter of which cannot be created by the corresponding aspartic acid in EPIYA-C. Thus, a variation in a single amino-acid residue determines the magnitude for the pathogenic/oncogenic action of CagA, which may influence the worldwide landscape in the incidence of H. pylori-associated malignancies, especially gastric cancer.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Akiba S, Koriyama C, Herrera-Goepfert R, Eizuru Y (2008) Epstein-Barr virus associated gastric carcinoma: epidemiological and clinicopathological features. Cancer Sci 99(2):195–201. https://doi.org/10.1111/j.1349-7006.2007.00674.x
Akopyants NS, Clifton SW, Kersulyte D, Crabtree JE, Youree BE, Reece CA, Bukanov NO, Drazek ES, Roe BA, Berg DE (1998) Analyses of the cag pathogenicity island of Helicobacter pylori. Mol Microbiol 28(1):37–53
Argent RH, Kidd M, Owen RJ, Thomas RJ, Limb MC, Atherton JC (2004) Determinants and consequences of different levels of CagA phosphorylation for clinical isolates of Helicobacter pylori. Gastroenterology 127(2):514–523. https://doi.org/10.1053/j.gastro.2004.06.006
Asahi M, Azuma T, Ito S, Ito Y, Suto H, Nagai Y, Tsubokawa M, Tohyama Y, Maeda S, Omata M, Suzuki T, Sasakawa C (2000) Helicobacter pylori CagA protein can be tyrosine phosphorylated in gastric epithelial cells. J Exp Med 191(4):593–602. PMC2195829
Azuma T, Yamakawa A, Yamazaki S, Fukuta K, Ohtani M, Ito Y, Dojo M, Yamazaki Y, Kuriyama M (2002) Correlation between variation of the 3′ region of the cagA gene in Helicobacter pylori and disease outcome in Japan. J Infect Dis 186(11):1621–1630. https://doi.org/10.1086/345374
Azuma T, Yamazaki S, Yamakawa A, Ohtani M, Muramatsu A, Suto H, Ito Y, Dojo M, Yamazaki Y, Kuriyama M, Keida Y, Higashi H, Hatakeyama M (2004) Association between diversity in the Src homology 2 domain-containing tyrosine phosphatase binding site of Helicobacter pylori CagA protein and gastric atrophy and cancer. J Infect Dis 189(5):820–827. https://doi.org/10.1086/381782
Backert S, Ziska E, Brinkmann V, Zimmy-Arndt U, Fauconnier A, Jungblut PR, Naumann M, Meyer T (2000) Translocation of the CagA protein in gastric epithelial cells by a type IV secretion apparatus. Cell Microbiol 2(2):155–164
Basso D, Zambon CF, Letley DP, Stranges A, Marchet A, Rhead JL, Schiavon S, Guariso G, Ceroti M, Nitti D, Rugge M, Plebani M, Atherton JC (2008) Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms. Gastroenterology 135(1):91–99. https://doi.org/10.1053/j.gastro.2008.03.041
Batista SA, Rocha GA, Rocha AM, Saraiva IE, Cabral MM, Oliveira RC, Queiroz DM (2011) Higher number of Helicobacter pylori CagA EPIYA C phosphorylation sites increases the risk of gastric cancer, but not duodenal ulcer. BMC Microbiol 11:61. https://doi.org/10.1186/1471-2180-11-61
Bautista-Quach MA, Ake CD, Chen M, Wang J (2012) Gastrointestinal lymphomas: Morphology, immunophenotype and molecular features. J Gastrointest Oncol 3(3):209–225. https://doi.org/10.3978/j.issn.2078-6891.2012.024
Beltrán-Anaya FO, Poblete TM, Román-Román A, Reyes S, deSampedro J, Peralta-Zaragoza O, Rodríguez MÁ, del Moral-Hernández O, Illades-Aguiar B, Fernández-Tilapa G (2014) The EPIYA-ABCC motif pattern in CagA of Helicobacter pylori is associated with peptic ulcer and gastric cancer in Mexican population. BMC Gastroenterol 14(223). https://doi.org/10.1186/s12876-014-0223-9
Bentires-Alj M, Paez JG, David FS, Keilhack H, Halmos B, Naoki K, Maris JM, Richardson A, Bardelli A, Sugarbaker DJ, Richards WG, Du J, Girard L, Minna JD, Loh ML, Fisher DE, Velculescu VE, Vogelstein B, Meyerson M, Sellers WR, Neel BG (2004) Activating mutations of the noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia. Cancer Res 64(24):8816–8820. https://doi.org/10.1158/0008-5472.CAN-04-1923
Blaser MJ, Perez-Perez GI, Kleanthous H, Cover TL, Peek RM, Chyou PH, Stemmermann GN, Nomura A (1995) Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the gastric cancer. Cancer Res 55(10):2111–2115
Buti L, Spooner E, Van der Veen AG, Rappuoli R, Covacci A, Ploegh HL (2011) 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(22):9238–9243. https://doi.org/10.1073/pnas.1106200108
Cave DR (1997) How is Helicobacter pylori transmitted? Gastroenterology 113(6):S9–S14. https://doi.org/10.1016/S0016-5085(97)80004-2
Censini S, Lange C, Xiang Z, Crabtree JE, Ghiara P, Borodovsky M, Rappuoli R, Covacci A (1996) cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci U S A 93(25):14648–14653. https://doi.org/PMC26189
Chang Y, Moore PS (2012) Merkel cell carcinoma: a virus-induced human cancer. Annu Rev Pathol 7:123–144. https://doi.org/10.1146/annurev-pathol-011110-130227
Covacci A, Censini S, Bugnoli M, Petracca R, Burroni D, Macchia G, Rappuoli R (1993) Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci U S A 90(12):5791–5795. PMC46808
Eck M, Schmausser B, Haas R, Greiner A, Czub S, Müller-Hermelink HK (1997) MALT-type lymphoma of the stomach is associated with Helicobacter pylori strains expressing the CagA protein. Gastroenterology 112(5):1482–1486
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386. https://doi.org/10.1002/ijc.29210
Ferreira Júnior M, Batista SA, Vidigal PV, Cordeiro AA, Oliveira FM, Prata LO, Diniz AE, Barral CM, Barbuto RC, Gomes AD, Araújo ID, Queiroz DM, Caliari MV (2015) Infection with CagA-positive Helicobacter pylori strain containing three EPIYA C phosphorylation sites is associated with more severe gastric lesions in experimentally infected Mongolian gerbils (Meriones unguiculatus). Eur J Histochem 59(2):2489. https://doi.org/10.4081/ejh.2015.2489
Forman D, Newell DG, Fullerton F, Yarnell JW, Stacey AR, Wald N, Sitas F (1991) Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation. BMJ 302(6788):1302–1305
Fukase K, Kato M, Kikuchi S, Inoue K, Uemura N, Okamoto S, Terao S, Amagai K, Hayashi S, Asaka M, Japan Gast Study Group (2008) Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet 372(9536):392–397. https://doi.org/10.1016/S0140-6736(08)61159-9
Gall A, Gaudet RG, Gray-Owen SD, Salama NR (2017) TIFA signaling in gastric epithelial cells initiates the cag type 4 secretion system-dependent innate immune response to Helicobacter pylori infection. MBio 8(4):e01168–e01117. https://doi.org/10.1128/mBio.01168-17
González I, Romero J, Rodríguez B, Llanos J, Morales E, Figueroa H, Perez-Castro R, Valdés E, Cofre C, Rojas A (2011) High prevalence of virulence-associated genotypes in Helicobacter pylori clinical isolates in the region del Maule, Chile. Scand J Infect Dis 43(8):652–655. https://doi.org/10.1016/j.micinf.2011.04.005
Hatakeyama M (2004) Oncogenic mechanisms of Helicobacter pylori CagA protein. Nat Rev Cancer 4(9):688–694. https://doi.org/10.1038/nrc1433
Hayashi T, Senda M, Morohashi H, Higashi H, Horio M, Kashiba Y, Nagase L, Sasaya D, Shimizu T, Venugopalan N, Kumeta H, Noda NN, Inagaki F, Senda T, Hatakeyama M (2012a) Tertiary structure-function analysis reveals the pathogenic signaling potentiation mechanism of Helicobacter pylori oncogenic effector CagA. Cell Host Microbe 12(1):20–33. https://doi.org/10.1016/j.chom.2012.05.010
Hayashi K, Suzuki A, Ohno S (2012b) PAR-1/MARK: a kinase essential for maintaining the dynamic state of microtubules. Cell Struct Funct 37(1):21–25
Hayashi D, Tamura A, Tanaka H, Yamazaki Y, Watanabe S, Suzuki K, Suzuki K, Sentani K, Yasui W, Rakugi H, Isaka Y, Tsukita S (2012c) Deficiency of claudin-18 causes paracellular H+ leakage, up-regulation of interleukin-1β, and atrophic gastritis in mice. Gastroenterology 142(2):292–304. https://doi.org/10.1053/j.gastro.2011.10.040
Hayashi T, Senda M, Suzuki N, Nishikawa H, Ben C, Tang C, Nagase L, Inoue K, Senda T, Hatakeyama M (2017) Differential mechanisms for SHP2 binding and activation are exploited by geographically distinct Helicobacter pylori CagA oncoproteins. Cell Rep 20(12):2876–2890. https://doi.org/10.1016/j.celrep.2017.08.080
Herrero R, Parsonnet J, Greenberg ER (2014) Prevalence of gastric cancer. JAMA 312(12):1197–1198. https://doi.org/10.1001/jama.2014.10498
Higashi H, Tsutsumi R, Fujita A, Yamazaki S, Asaka M, Azuma T, Hatakeyama M (2002a) 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(22):14428–14433. https://doi.org/10.1073/pnas.222375399
Higashi H, Tsutsumi R, Muto S, Sugiyama T, Azuma T, Asaka M, Hatakeyama M (2002b) SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science 295(5555):683–686. https://doi.org/10.1126/science.1067147
Huang JQ, Zheng GF, Sumanac K, Irvine EJ, Hunt RH (2003) Meta-analysis of the relationship between cagA seropositivity and gastric cancer. Gastroenterology 125(6):1636–1644
Ito Y, Azuma T, Ito S, Miyaji H, Hirai M, Yamazaki Y, Sato F, Kato T, Kohli Y, Kuriyama M (1997) Analysis and typing of the vacA gene from cagA-positive strains of Helicobacter pylori isolated in Japan. J Clin Microbiol 35(7):1710–1714
Kaplan-Türköz B, Jiménez-Soto LF, Dian C, Ertl C, Remaut H, Louche A, Tosi T, Haas R, Terradot L (2012) Structural insights into Helicobacter pylori oncoprotein CagA interaction with β1 integrin. Proc Natl Acad Sci U S A 109(36):14640–14645. https://doi.org/10.1073/pnas.1206098109
Kuipers EJ, Pérez-Pérez GI, Meuwissen SG, Blaser MJ (1995) Helicobacter pylori and atrophic gastritis: importance of the cagA status. J Natl Cancer Inst 87(23):1777–1780
Kuo SH, Chen LT, Lin CW, Wu MS, Hsu PN, Tsai HJ, Chu CY, Tzeng YS, Wang HP, Yeh KH, Cheng AL (2013) Detection of the Helicobacter pylori CagA protein in gastric mucosa-associated lymphoid tissue lymphoma cells: clinical and biological significance. Blood Cancer J 3:e125. https://doi.org/10.1038/bcj.2013.22
Lee DG, Kim HS, Lee YS, Kim S, Cha SY, Ota I, Kim NH, Cha YH, Yang DH, Lee Y, Park GJ, Yook JI, Lee YC (2014) Helicobacter pylori CagA promotes Snail-mediated epithelial-mesenchymal transition by reducing GSK-3 activity. Nat Commun 5(4423). https://doi.org/10.1038/ncomms5423
Lin WC, Tsai HF, Kuo SH, Wu MS, Lin CW, Hsu PI, Cheng AL, Hsu PN (2010) Translocation of Helicobacter pylori CagA into human B lymphocytes, the origin of mucosa-associated lymphoid tissue lymphoma. Cancer Res 70(14):5740–5748. https://doi.org/10.1158/0008-5472.CAN-09-4690
Lu H, Saito Y, Umeda M, Murata-Kamiya N, Zhang H, Higashi H, Hatakeyama M (2008) Structural and functional diversity in the PAR1b/MARK2-binding region of Helicobacter pylori CagA. Cancer Sci 99(10):2004–2011. https://doi.org/10.1111/j.1349-7006.2008.00950.x
Matenia D, Mandelkow EM (2009) The tau of MARK: a polarized view of the cytoskeleton. Trends Biochem Sci 34(7):332–342. https://doi.org/10.1016/j.tibs.2009.03.008
Matsuo T, Ito M, Takata S, Tanaka S, Yoshihara M, Chayama K (2011) Low prevalence of Helicobacter pylori-negative gastric cancer among Japanese. Helicobacter 16(6):415–419. https://doi.org/10.1111/j.1523-5378.2011.00889.x
Matsusaka K, Funata S, Fukayama M, Kaneda A (2014) DNA methylation in gastric cancer, related to Helicobacter pylori and Epstein-Barr virus. World J Gastroenterol 20(14):3916–3926. https://doi.org/10.3748/wjg.v20.i14.3916
Mimuro H, Suzuki T, Tanaka J, Asahi M, Haas R, Sasakawa C (2002) Grb2 is a key mediator of Helicobacter pylori CagA protein activities. Mol Cell 10(4):745–755
Murata-Kamiya N, Kurashima Y, Teishikata Y, Yamahashi Y, Saito Y, Higashi H, Aburatani H, Akiyama T, Peek RMJR, Azuma T, Hatakeyama M (2007) Helicobacter pylori CagA interacts with E-cadherin and deregulates the β-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells. Oncogene 26(32):4617–4626. https://doi.org/10.1038/sj.onc.1210251
Murata-Kamiya N, Kikuchi K, Hayashi T, Higashi H, Hatakeyama M (2010) Helicobacter pylori exploits host membrane phosphatidylserine for delivery, localization and pathophysiological action of the CagA oncoprotein. Cell Host Microbe 7(5):399–411. https://doi.org/10.1016/j.chom.2010.04.005
Nagase L, Hayashi T, Senda T, Hatakeyama M (2015) Dramatic increase in SHP2 binding activity of Helicobacter pylori Western CagA by EPIYA-C duplication: its implications in gastric carcinogenesis. Sci Rep 5:15749. https://doi.org/10.1038/srep15749
Neal JT, Peterson TS, Kent ML, Guillemin K (2013) H. pylori virulence factor CagA increases intestinal cell proliferation by Wnt pathway activation in a transgenic zebrafish model. Dis Model Mech 6(3):802–810. https://doi.org/10.1242/dmm.011163
Neel BG, Gu H, Pao L (2003) The ‘Shp’ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends Biochem Sci 28(6):284–293. https://doi.org/10.1016/S0968-0004(03)00091-4
Nemati M, Larussa T, Khorramdelazad H, Mahmoodi M, Jafarzadeh A (2017) Toll-like receptor 2: An important immunomodulatory molecule during Helicobacter pylori infection. Life Sci 178:17–29. https://doi.org/10.1016/j.lfs.2017.04.006
Nesić D, Miller MC, Quinkert ZT, Stein M, Chait BT, Stebbins CE (2010) Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates. Nat Struct Mol Biol 17(1):130–132. https://doi.org/10.1038/nsmb.1705
Nishikawa H, Hayashi T, Arisaka F, Senda T, Hatakeyama M (2016) Impact of structural polymorphism for the Helicobacter pylori CagA oncoprotein on binding to polarity-regulating kinase PAR1b. Sci Rep 6:30031. https://doi.org/10.1038/srep30031
Nomura A, Stemmermann GN, Chyou PH, Kato I, Perez-Perez GI, Blaser MJ (1991) Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med 325(16):1132–1136. https://doi.org/10.1056/NEJM199110173251604
Odenbreit S, Puls J, Sedlmaier B, Gerland E, Fischer W, Haas R (2000) Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science 287(5457):1497–1500
Ohnishi N, Yuasa H, Tanaka S, Sawa H, Miura M, Matsui A, Higashi H, Musashi M, Iwabuchi K, Suzuki M, Yamada G, Azuma T, Hatakeyama M (2008) Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc Natl Acad Sci U S A 105(3):1003–1008. https://doi.org/10.1073/pnas.0711183105
Ono S, Kato M, Suzuki M, Ishigaki S, Takahashi M, Haneda M, Mabe K, Shimizu Y (2012) Frequency of Helicobacter pylori-negative gastric cancer and gastric mucosal atrophy in a Japanese endoscopic submucosal dissection series including histological, endoscopic and serological atrophy. Digestion 86(1):59–65. https://doi.org/10.1159/000339176
Park JY, Forman D, Waskito LA, Yamaoka Y, Crabtree JE (2018) Epidemiology of Helicobacter pylori and CagA-positive infections and global variations in gastric cancer. Toxins 10(4):163. https://doi.org/10.3390/toxins10040163
Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, Sibley RK (1991) Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 325(16):1127–1131. https://doi.org/10.1056/NEJM199110173251603
Parsonnet J, Friedman GD, Orentreich N, Vogelman H (1997) Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection. Gut 40(3):297–301. PMC1027076
Plummer M, de MArtel C, Vignat J, Ferlay J, Bray F, Franceschi S (2016) Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Glob Health 4(9):e609–e616. https://doi.org/10.1016/S2214-109X(16)30143-7
Poppe M, Feller SM, Römer G, Wessler S (2007) Phosphorylation of Helicobacter pylori CagA by c-Abl leads to cell motility. Oncogene 26(24):3462–3472. https://doi.org/10.1038/sj.onc.1210139
Ren S, Higashi H, Lu H, Azuma T, Hatakeyama M (2006) Structural basis and functional consequence of Helicobacter pylori CagA multimerization in Cells. J Biol Chem 281(43):32344–32352. https://doi.org/10.1074/jbc.M606172200
Rieder G, Merchant JL, Haas R (2005) Helicobacter pylori cag-type IV secretion system facilitates corpus colonization to induce precancerous conditions in Mongolian gerbils. Gastroenterology 128(5):1229–1242
Saadat I, Higashi H, Obuse C, Umeda M, Murata-Kamiya N, Saito Y, Lu H, Ohnishi N, Azuma T, Suzuki A, Ohno S, Hatakeyama M (2007) Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity. Nature 447(7142):330–333. https://doi.org/10.1038/nature05765
Saju P, Murata-Kamiya N, Hayashi T, Senda Y, Nagase L, Noda S, Matsusaka K, Funata S, Kunita A, Urabe M, Seto Y, Fukayama M, Kaneda A, Hatakeyama M (2016) Host SHP1 phosphatase antagonizes Helicobacter pylori CagA and can be downregulated by Epstein-Barr virus. Nat Microbiol 1:16026. https://doi.org/10.1038/nmicrobiol.2016.26
Satomi S, Yamakawa A, Matsunaga S, Masaki R, Inagaki T, Okuda T, Suto H, Ito Y, Yamazaki Y, Kuriyama M, Keida Y, Kutsumi H, Azuma T (2006) Relationship between the diversity of the cagA gene of Helicobacter pylori and gastric cancer in Okinawa, Japan. J Gastroenterol 41(7):668–673. https://doi.org/10.1007/s00535-006-1838-6
Segal ED, Cha J, Lo J, Falkow S, Tompkins LS (1999) 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(25):14559–14564. PMC24475
Selbach M, Moese S, Hauck CR, Meyer TF, Backert S (2002) Src is the kinase of the Helicobacter pylori CagA protein in vitro and in vivo. J Biol Chem 277(9):6775–6778. https://doi.org/10.1074/jbc.C100754200
Selbach M, Paul FE, Brandt S, Guye P, Daumke O, Backert S, Dehio C, Mann M (2009) Host cell interactome of tyrosine-phosphorylated bacterial proteins. Cell Host Microbe 5(4):397–403. https://doi.org/10.1016/j.chom.2009.03.004
Sicinschi LA, Correa P, Peek RM, Camargo MC, Piazuelo MB, Romero-Gallo J, Hobbs SS, Krishna U, Delgado A, Mera R, Bravo LE, Schneider BG (2010) CagA C-terminal variations in Helicobacter pylori strains from Colombian patients with gastric precancerous lesions. Clin Microbiol Infect 16(4):369–378. https://doi.org/10.1111/j.1469-0691.2009.02811.x
Stein M, Rappuoli R, Covacci A (2000) Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation. Proc Natl Acad Sci U S A 97(3):1263–1268. PMC15590
Stein M, Bagnoli F, Halenbeck R, Rappuoli R, Fantl WJ, Covacci A (2002) c-Src/Lyn kinases activate Helicobacter pylori CagA through tyrosine phosphorylation of the EPIYA motifs. Mol Microbiol 43(4):971–980. https://doi.org/10.1046/j.1365-2958.2002.02781.x
Stein SC, Faber E, Bats SH, Murillo T, Speidel Y, Coombs N, Josenhans C (2017) Helicobacter pylori modulates host cell responses by CagT4SS-dependent translocation of an intermediate metabolite of LPS inner core heptose biosynthesis. PLoS Pathog 13(7):e1006514. https://doi.org/10.1371/journal.ppat.1006514
Suzuki M, Mimuro H, Suzuki T, Park M, Yamamoto T, Sasakawa C (2005) Interaction of CagA with Crk plays an important role in Helicobacter pylori-induced loss of gastric epithelial cell adhesion. J Exp Med 202(9):1235–1247. https://doi.org/10.1084/jem.20051027
Suzuki M, Mimuro H, Kiga K, Fukumatsu M, Ishijima N, Morikawa H, Nagai S, Koyasu S, Gilman RH, Kersulyte D, Berg DE, Sasakawa C (2009) Helicobacter pylori CagA phosphorylation-independent function in epithelial proliferation and inflammation. Cell Host Microbe 5(1):23–34. https://doi.org/10.1016/j.chom.2008.11.010
Suzuki N, Murata-Kamiya N, Yanagiya K, Suda W, Hattori M, Kanda H, Bingo A, Fujii Y, Maeda S, Koike K, Hatakeyama M (2015) Mutual reinforcement of inflammation and carcinogenesis by the Helicobacter pylori CagA oncoprotein. Sci Rep 5:10024. https://doi.org/10.1038/srep10024
Tammer I, Brandt S, Hartig R, König W, Backert S (2007) Activation of Abl by Helicobacter pylori: a novel kinase for CagA and crucial mediator of host cell scattering. Gastroenterology 132(4):1309–1319. https://doi.org/10.1053/j.gastro.2007.01.050
Tartaglia M, Niemeyer CM, Fragale A, Song X, Buechner J, Jung A, Hählen K, Hasle H, Licht JD, Gelb BD (2003) Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nat Genet 34(2):148–150. https://doi.org/10.1038/ng1156
Troppan K, Wenzl K, Neumeister P, Deutsch A (2015) Molecular pathogenesis of MALT lymphoma. Gastroenterol Res Pract 2015:102656. https://doi.org/10.1155/2015/102656
Tsang YH, Lamb A, Romero-Gallo J, Huang B, Ito K, Peek RM Jr, Ito Y, Chen LF (2010) Helicobacter pylori CagA targets gastric tumor suppressor RUNX3 for proteasome-mediated degradation. Oncogene 29(41):5643–5650. https://doi.org/10.1038/onc.2010.304
Tummuru MK, Cover TL, Blaser MJ (1993) Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. Infect Immun 61(5):1799–1809. PMC280768
Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ (2001) Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 345(11):784–789. https://doi.org/10.1056/NEJMoa001999
Umehara S, Higashi H, Ohnishi N, Asaka M, Hatakeyama M (2003) Effects of Helicobacter pylori CagA protein on the growth and survival of B lymphocytes, the origin of MALT lymphoma. Oncogene 22(51):8337–8342. https://doi.org/10.1038/sj.onc.1207028
Viala J, Chaput C, Boneca IG, Cardona A, Girardin SE, Moran AP, Athman R, Mémet S, Huerre MR, Coyle AJ, DiStefano PS, Sansonetti PJ, Labigne A, Bertin J, Philpott DJ, Ferrero RL (2004) Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat Immunol 5(11):1166–1174. https://doi.org/10.1038/ni1131
Vilaichone RK, Mahachai V, Tumwasorn S, Wu JY, Graham DY, Yamaoka Y (2004) Molecular epidemiology and outcome of Helicobacter pylori infection in Thailand: a cultural cross roads. Helicobacter 9(5):453–459. https://doi.org/10.1111/j.1083-4389.2004.00260.x
Warren JR, Marshall B (1983) Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1(8390):1273–1275. https://doi.org/10.1016/S0140-6736(83)92719-8
Wei J, Noto JM, Zaika E, Romero-Gallo J, Piazuelo MB, Schneider B, El-Rifai W, Correa P, Peek RM, Zaika AI (2015) Bacterial CagA protein induces degradation of p53 protein in a p14ARF-dependent manner. Gut 64(7):1040–1048. https://doi.org/10.1136/gutjnl-2014-307295
Wong BC, Lam SK, Wong WM, Chen JS, Zheng TT, Feng RE, Lai KC, Hu WH, Yuen ST, Leung SY, Fong DY, Ho J, Ching CK, Chen JS, China Gastric Cancer Study Group (2004) Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA 291(12):187–194. https://doi.org/10.1001/jama.291.2.187
Wu CY, Kuo KN, Wu MS, Chen YJ, Wang CB, Lin JT (2009) Early Helicobacter pylori eradication decreases risk of gastric cancer in patients with peptic ulcer disease. Gastroenterology 137(5):1641–1648. https://doi.org/10.1053/j.gastro.2009.07.060
Xia Y, Yamaoka Y, Zhu Q, Matha I, Gao X (2009) A comprehensive sequence and disease correlation analyses for the C-terminal region of CagA protein of Helicobacter pylori. PLoS One 4(11):e7736. https://doi.org/10.1371/journal.pone.0007736
Zeaiter Z, Cohen D, Müsch A, Bagnoli F, Covacci A, Stein M (2008) 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(3):781–794. https://doi.org/10.1111/j.1462-5822.2007.01084.x
Zhou P, She Y, Dong N, Li P, He H, Borio A, Wu Q, Lu S, Ding X, Cao Y, Xu Y, Gao W, Dong M, Ding J, Wang DC, Zamyatina A, Shao F (2018) Alpha-kinase 1 is a cytosolic innate immune receptor for bacterial ADP-heptose. Nature 561(7721):122–126. https://doi.org/10.1038/s41586-018-0433-3
Zimmermann S, Pfannkuch L, Al-Zeer MA, Bartfeld S, Koch M, Liu J, Rechner C, Soerensen M, Sokolova O, Zamyatina A, Kosma P, Mäurer AP, Glowinski F, Pleissner KP, Schmid M, Brinkmann V, Karlas A, Naumann M, Rother M, Machuy N, Meyer TF (2017) ALPK1- and TIFA-dependent innate immune response triggered by the Helicobacter pylori Type IV secretion system. Cell Rep 20(10):2384–2395. https://doi.org/10.1016/j.celrep.2017.08.039
Zullo A, Hassan C, Ridola L, Repici A, Manta R, Andriani A (2014) Gastric MALT lymphoma: old and new insights. Ann Gastroenterol 27(1):27–33. PMC3959547
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Hatakeyama, M. (2019). Malignant Helicobacter pylori-Associated Diseases: Gastric Cancer and MALT Lymphoma. In: Kamiya, S., Backert, S. (eds) Helicobacter pylori in Human Diseases. Advances in Experimental Medicine and Biology(), vol 1149. Springer, Cham. https://doi.org/10.1007/5584_2019_363
Download citation
DOI: https://doi.org/10.1007/5584_2019_363
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-21915-4
Online ISBN: 978-3-030-21916-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)