Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
December-2016 Volume 36 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2016 Volume 36 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review

Pathogenic mechanisms of the oncoprotein CagA in H. pylori-induced gastric cancer (Review)

  • Authors:
    • Shuai-Yin Chen
    • Rong-Guang Zhang
    • Guang-Cai Duan
  • View Affiliations / Copyright

    Affiliations: Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
  • Pages: 3087-3094
    |
    Published online on: October 4, 2016
       https://doi.org/10.3892/or.2016.5145
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Infection with Helicobacter pylori is the strongest risk factor for the development of chronic gastritis, gastric ulcer and gastric carcinoma. The majority of the H. pylori-infected population remains asymptomatic, and only 1% of individuals may progress to gastric cancer. The clinical outcomes caused by H. pylori infection are considered to be associated with bacterial virulence, genetic polymorphism of hosts as well as environmental factors. Most H. pylori strains possess a cytotoxin-associated gene (cag) pathogenicity island (cagPAI), encoding a 120-140 kDa CagA protein, which is the most important bacterial oncoprotein. CagA is translocated into host cells via T4SS system and affects the expression of signaling proteins in a phosphorylation-dependent and independent manner. Thus, this review summarizes the results of relevant studies, discusses the pathogenesis of CagA-mediated gastric cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Pacchiani N, Censini S, Buti L and Covacci A: Echoes of a distant past: The cag pathogenicity island of Helicobacter pylori. Cold Spring Harb Perspect Med. 3:a0103552013. View Article : Google Scholar : PubMed/NCBI

2 

Cavaleiro-Pinto M, Peleteiro B, Lunet N and Barros H: Helicobacter pylori infection and gastric cardia cancer: Systematic review and meta-analysis. Cancer Causes Control. 22:375–387. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Akopyants NS, Clifton SW, Kersulyte D, Crabtree JE, Youree BE, Reece CA, Bukanov NO, Drazek ES, Roe BA and Berg DE: Analyses of the cag pathogenicity island of Helicobacter pylori. Mol Microbiol. 28:37–53. 1998. View Article : Google Scholar : PubMed/NCBI

4 

Censini S, Lange C, Xiang Z, Crabtree JE, Ghiara P, Borodovsky M, Rappuoli R and Covacci A: cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci USA. 93:14648–14653. 1996. View Article : Google Scholar : PubMed/NCBI

5 

Yamaoka Y: Helicobacter pylori typing as a tool for tracking human migration. Clin Microbiol Infect. 15:829–834. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Lai CH, Perng CL, Lan KH and Lin HJ: Association of IS605 and cag-PAI of Helicobacter pylori isolated from patients with gastrointestinal diseases in Taiwan. Gastroenterol Res Pract. 2013:3562172013. View Article : Google Scholar : PubMed/NCBI

7 

Torres J, Perez-Perez GI, Leal-Herrera Y and Munoz O: Infection with CagA+ Helicobacter pylori strains as a possible predictor of risk in the development of gastric adenocarcinoma in Mexico. Int J Cancer. 78:298–300. 1998. View Article : Google Scholar : PubMed/NCBI

8 

Batista SA, Rocha GA, Rocha AM, Saraiva IE, Cabral MM, Oliveira RC and Queiroz DM: Higher number of Helicobacter pylori CagA EPIYA C phosphorylation sites increases the risk of gastric cancer, but not duodenal ulcer. BMC Microbiol. 11:612011. View Article : Google Scholar : PubMed/NCBI

9 

Franco AT, Johnston E, Krishna U, Yamaoka Y, Israel DA, Nagy TA, Wroblewski LE, Piazuelo MB, Correa P and Peek RM Jr: Regulation of gastric carcinogenesis by Helicobacter pylori virulence factors. Cancer Res. 68:379–387. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Ohnishi N, Yuasa H, Tanaka S, Sawa H, Miura M, Matsui A, Higashi H, Musashi M, Iwabuchi K, Suzuki M, et al: Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc Natl Acad Sci USA. 105:1003–1008. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Backert S, Tegtmeyer N and Fischer W: Composition, structure and function of the Helicobacter pylori cag pathogenicity island encoded type IV secretion system. Future Microbiol. 10:955–965. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Tegtmeyer N, Hartig R, Delahay RM, Rohde M, Brandt S, Conradi J, Takahashi S, Smolka AJ, Sewald N and Backert S: A small fibronectin-mimicking protein from bacteria induces cell spreading and focal adhesion formation. J Biol Chem. 285:23515–23526. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Murata-Kamiya N, Kikuchi K, Hayashi T, Higashi H and Hatakeyama M: Helicobacter pylori exploits host membrane phosphatidylserine for delivery, localization, and pathophysiological action of the CagA oncoprotein. Cell Host Microbe. 7:399–411. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Fischer W: Assembly and molecular mode of action of the Helicobacter pylori Cag type IV secretion apparatus. FEBS J. 278:1203–1212. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Gopal GJ, Pal J, Kumar A and Mukhopadhyay G: C-terminal domain of CagX is responsible for its interaction with CagT protein of Helicobacter pylori type IV secretion system. Biochem Biophys Res Commun. 456:98–103. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Shariq M, Kumar N, Kumari R, Kumar A, Subbarao N and Mukhopadhyay G: Biochemical analysis of CagE: A VirB4 homologue of Helicobacter pylori Cag-T4SS. PLoS One. 10:e01426062015. View Article : Google Scholar : PubMed/NCBI

17 

Odenbreit S, Püls J, Sedlmaier B, Gerland E, Fischer W and Haas R: Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science. 287:1497–1500. 2000. View Article : Google Scholar : PubMed/NCBI

18 

Schindele F, Weiss E, Haas R and Fischer W: Quantitative analysis of CagA type IV secretion by Helicobacter pylori reveals substrate recognition and translocation requirements. Mol Microbiol. 100:188–203. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Stein M, Bagnoli F, Halenbeck R, Rappuoli R, Fantl WJ and Covacci A: c-Src/Lyn kinases activate Helicobacter pylori CagA through tyrosine phosphorylation of the EPIYA motifs. Mol Microbiol. 43:971–980. 2002. View Article : Google Scholar : PubMed/NCBI

20 

Tegtmeyer N and Backert S: Role of Abl and Src family kinases in actin-cytoskeletal rearrangements induced by the Helicobacter pylori CagA protein. Eur J Cell Biol. 90:880–890. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Tammer I, Brandt S, Hartig R, König W and Backert S: Activation of Abl by Helicobacter pylori: A novel kinase for CagA and crucial mediator of host cell scattering. Gastroenterology. 132:1309–1319. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Zhu Y-L, Zheng S, Du Q, Qian K-D and Fang P-C: Characterization of CagA variable region of Helicobacter pylori isolates from Chinese patients. World J Gastroenterol. 11:880–884. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Vaziri F, Peerayeh SN, Alebouyeh M, Maghsoudi N, Azimzadeh P, Siadat SD and Zali MR: Novel effects of Helicobacter pylori CagA on key genes of gastric cancer signal transduction: A comparative transfection study. Pathog Dis. 73:ftu0212015. View Article : Google Scholar : PubMed/NCBI

24 

Zhang XS, Tegtmeyer N, Traube L, Jindal S, Perez-Perez G, Sticht H, Backert S and Blaser MJ: A specific A/T polymorphism in Western tyrosine phosphorylation B-motifs regulates Helicobacter pylori CagA epithelial cell interactions. PLoS Pathog. 11:e10046212015. View Article : Google Scholar : PubMed/NCBI

25 

Ferreira RM, Machado JC, Leite M, Carneiro F and Figueiredo C: The number of Helicobacter pylori CagA EPIYA C tyrosine phosphorylation motifs influences the pattern of gastritis and the development of gastric carcinoma. Histopathology. 60:992–998. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Higashi H, Tsutsumi R, Fujita A, Yamazaki S, Asaka M, Azuma T and Hatakeyama M: Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc Natl Acad Sci USA. 99:14428–14433. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Monstein H-J, Karlsson A, Ryberg A and Borch K: Application of PCR amplicon sequencing using a single primer pair in PCR amplification to assess variations in Helicobacter pylori CagA EPIYA tyrosine phosphorylation motifs. BMC Res Notes. 3:352010. View Article : Google Scholar : PubMed/NCBI

28 

De Souza D, Fabri LJ, Nash A, Hilton DJ, Nicola NA and Baca M: SH2 domains from suppressor of cytokine signaling-3 and protein tyrosine phosphatase SHP-2 have similar binding specificities. Biochemistry. 41:9229–9236. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Mueller D, Tegtmeyer N, Brandt S, Yamaoka Y, De Poire E, Sgouras D, Wessler S, Torres J, Smolka A and Backert S: 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. 122:1553–1566. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Ren S, Higashi H, Lu H, Azuma T and Hatakeyama M: Structural basis and functional consequence of Helicobacter pylori CagA multimerization in cells. J Biol Chem. 281:32344–32352. 2006. View Article : Google Scholar : PubMed/NCBI

31 

Yamazaki S, Yamakawa A, Ito Y, Ohtani M, Higashi H, Hatakeyama M and Azuma T: The CagA protein of Helicobacter pylori is translocated into epithelial cells and binds to SHP-2 in human gastric mucosa. J Infect Dis. 187:334–337. 2003. View Article : Google Scholar : PubMed/NCBI

32 

Montagner A, Yart A, Dance M, Perret B, Salles JP and Raynal P: A novel role for Gab1 and SHP2 in epidermal growth factor-induced Ras activation. J Biol Chem. 280:5350–5360. 2005. View Article : Google Scholar : PubMed/NCBI

33 

Higashi H, Nakaya A, Tsutsumi R, Yokoyama K, Fujii Y, Ishikawa S, Higuchi M, Takahashi A, Kurashima Y, Teishikata Y, et al: Helicobacter pylori CagA induces Ras-independent morphogenetic response through SHP-2 recruitment and activation. J Biol Chem. 279:17205–17216. 2004. View Article : Google Scholar : PubMed/NCBI

34 

Tsutsumi R, Takahashi A, Azuma T, Higashi H and Hatakeyama M: Focal adhesion kinase is a substrate and downstream effector of SHP-2 complexed with Helicobacter pylori CagA. Mol Cell Biol. 26:261–276. 2006. View Article : Google Scholar : PubMed/NCBI

35 

Tsutsumi R, Higashi H, Higuchi M, Okada M and Hatakeyama M: Attenuation of Helicobacter pylori CagA × SHP-2 signaling by interaction between CagA and C-terminal Src kinase. J Biol Chem. 278:3664–3670. 2003. View Article : Google Scholar : PubMed/NCBI

36 

Suzuki M, Mimuro H, Suzuki T, Park M, Yamamoto T and Sasakawa C: Interaction of CagA with Crk plays an important role in Helicobacter pylori-induced loss of gastric epithelial cell adhesion. J Exp Med. 202:1235–1247. 2005. View Article : Google Scholar : PubMed/NCBI

37 

Bauer B, Pang E, Holland C, Kessler M, Bartfeld S and Meyer TF: The Helicobacter pylori virulence effector CagA abrogates human β-defensin 3 expression via inactivation of EGFR signaling. Cell Host Microbe. 11:576–586. 2012. View Article : Google Scholar : PubMed/NCBI

38 

Patel SR, Smith K, Letley DP, Cook KW, Memon AA, Ingram RJ, Staples E, Backert S, Zaitoun AM, Atherton JC, et al: Helicobacter pylori downregulates expression of human β-defensin 1 in the gastric mucosa in a type IV secretion-dependent fashion. Cell Microbiol. 15:2080–2092. 2013. View Article : Google Scholar : PubMed/NCBI

39 

Churin Y, Al-Ghoul L, Kepp O, Meyer TF, Birchmeier W and Naumann M: Helicobacter pylori CagA protein targets the c-Met receptor and enhances the motogenic response. J Cell Biol. 161:249–255. 2003. View Article : Google Scholar : PubMed/NCBI

40 

Suzuki M, Mimuro H, Kiga K, Fukumatsu M, Ishijima N, Morikawa H, Nagai S, Koyasu S, Gilman RH, Kersulyte D, et al: Helicobacter pylori CagA phosphorylation-independent function in epithelial proliferation and inflammation. Cell Host Microbe. 5:23–34. 2009. View Article : Google Scholar : PubMed/NCBI

41 

Mimuro H, Suzuki T, Tanaka J, Asahi M, Haas R and Sasakawa C: Grb2 is a key mediator of Helicobacter pylori CagA protein activities. Mol Cell. 10:745–755. 2002. View Article : Google Scholar : PubMed/NCBI

42 

Amieva MR, Vogelmann R, Covacci A, Tompkins LS, Nelson WJ and Falkow S: Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science. 300:1430–1434. 2003. View Article : Google Scholar : PubMed/NCBI

43 

Murata-Kamiya N, Kurashima Y, Teishikata Y, Yamahashi Y, Saito Y, Higashi H, Aburatani H, Akiyama T, Peek RM Jr, Azuma T, et al: Helicobacter pylori CagA interacts with E-cadherin and deregulates the β-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells. Oncogene. 26:4617–4626. 2007. View Article : Google Scholar : PubMed/NCBI

44 

Neal JT, Peterson TS, Kent ML and Guillemin K: H. pylori virulence factor CagA increases intestinal cell proliferation by Wnt pathway activation in a transgenic zebrafish model. Dis Model Mech. 6:802–810. 2013. View Article : Google Scholar : PubMed/NCBI

45 

Oliveira MJ, Costa AM, Costa AC, Ferreira RM, Sampaio P, Machado JC, Seruca R, Mareel M and Figueiredo C: CagA associates with c-Met, E-cadherin, and p120-catenin in a multiproteic complex that suppresses Helicobacter pylori-induced cell-invasive phenotype. J Infect Dis. 200:745–755. 2009. View Article : Google Scholar : PubMed/NCBI

46 

Kurashima Y, Murata-Kamiya N, Kikuchi K, Higashi H, Azuma T, Kondo S and Hatakeyama M: Deregulation of beta-catenin signal by Helicobacter pylori CagA requires the CagA-multimerization sequence. Int J Cancer. 122:823–831. 2008. View Article : Google Scholar : PubMed/NCBI

47 

Saadat I, Higashi H, Obuse C, Umeda M, Murata-Kamiya N, Saito Y, Lu H, Ohnishi N, Azuma T, Suzuki A, et al: Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity. Nature. 447:330–333. 2007. View Article : Google Scholar : PubMed/NCBI

48 

Goldstein B and Macara IG: The PAR proteins: Fundamental players in animal cell polarization. Dev Cell. 13:609–622. 2007. View Article : Google Scholar : PubMed/NCBI

49 

Suzuki A and Ohno S: The PAR-aPKC system: Lessons in polarity. J Cell Sci. 119:979–987. 2006. View Article : Google Scholar : PubMed/NCBI

50 

Lu HS, Saito Y, Umeda M, Murata-Kamiya N, Zhang HM, Higashi H and Hatakeyama M: Structural and functional diversity in the PAR1b/MARK2-binding region of Helicobacter pylori CagA. Cancer Sci. 99:2004–2011. 2008.PubMed/NCBI

51 

Lu H, Murata-Kamiya N, Saito Y and Hatakeyama M: Role of partitioning-defective 1/microtubule affinity-regulating kinases in the morphogenetic activity of Helicobacter pylori CagA. J Biol Chem. 284:23024–23036. 2009. View Article : Google Scholar : PubMed/NCBI

52 

Zeaiter Z, Cohen D, Müsch A, Bagnoli F, Covacci A and Stein M: 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. 10:781–794. 2008. View Article : Google Scholar : PubMed/NCBI

53 

Yamahashi Y and Hatakeyama M: PAR1b takes the stage in the morphogenetic and motogenetic activity of Helicobacter pylori CagA oncoprotein. Cell Adhes Migr. 7:11–18. 2013. View Article : Google Scholar

54 

Suzuki N, Murata-Kamiya N, Yanagiya K, Suda W, Hattori M, Kanda H, Bingo A, Fujii Y, Maeda S, Koike K, et al: Mutual reinforcement of inflammation and carcinogenesis by the Helicobacter pylori CagA oncoprotein. Sci Rep. 5:100242015. View Article : Google Scholar : PubMed/NCBI

55 

Mishra JP, Cohen D, Zamperone A, Nesic D, Muesch A and Stein M: CagA of Helicobacter pylori interacts with and inhibits the serine-threonine kinase PRK2. Cell Microbiol. 17:1670–1682. 2015. View Article : Google Scholar : PubMed/NCBI

56 

Sandoval J and Esteller M: Cancer epigenomics: Beyond genomics. Curr Opin Genet Dev. 22:50–55. 2012. View Article : Google Scholar : PubMed/NCBI

57 

Verma M: The role of epigenomics in the study of cancer biomarkers and in the development of diagnostic tools. Adv Exp Med Biol. 867:59–80. 2015. View Article : Google Scholar : PubMed/NCBI

58 

Hernando-Herraez I, Garcia-Perez R, Sharp AJ and Marques-Bonet T: DNA methylation: Insights into human evolution. PLoS Genet. 11:e10056612015. View Article : Google Scholar : PubMed/NCBI

59 

Maekita T, Nakazawa K, Mihara M, Nakajima T, Yanaoka K, Iguchi M, Arii K, Kaneda A, Tsukamoto T, Tatematsu M, et al: High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res. 12:989–995. 2006. View Article : Google Scholar : PubMed/NCBI

60 

Yoshida T, Kato J, Maekita T, Yamashita S, Enomoto S, Ando T, Niwa T, Deguchi H, Ueda K, Inoue I, et al: Altered mucosal DNA methylation in parallel with highly active Helicobacter pylori-related gastritis. Gastric Cancer. 16:488–497. 2013. View Article : Google Scholar : PubMed/NCBI

61 

Tomita H, Takaishi S, Menheniott TR, Yang X, Shibata W, Jin G, Betz KS, Kawakami K, Minamoto T and Tomasetto C: Inhibition of gastric carcinogenesis by the hormone gastrin is mediated by suppression of TFF1 epigenetic silencing. Gastroenterology. 140:879–891. 2011. View Article : Google Scholar : PubMed/NCBI

62 

Guo XB, Guo L, Zhi QM, Ji J, Jiang JL, Zhang RJ, Zhang JN, Zhang J, Chen XH, Cai Q, et al: Helicobacter pylori induces promoter hypermethylation and downregulates gene expression of IRX1 transcription factor on human gastric mucosa. J Gastroenterol Hepatol. 26:1685–1690. 2011. View Article : Google Scholar : PubMed/NCBI

63 

Hayashi Y, Tsujii M, Wang J, Kondo J, Akasaka T, Jin Y, Li W, Nakamura T, Nishida T, Iijima H, et al: CagA mediates epigenetic regulation to attenuate let-7 expression in Helicobacter pylori-related carcinogenesis. Gut. 62:1536–1546. 2013. View Article : Google Scholar : PubMed/NCBI

64 

Zhang YW, Eom SY, Yim DH, Song YJ, Yun HY, Park JS, Youn SJ, Kim BS, Kim YD and Kim H: Evaluation of the relationship between dietary factors, CagA-positive Helicobacter pylori infection, and RUNX3 promoter hypermethylation in gastric cancer tissue. World J Gastroenterol. 19:1778–1787. 2013. View Article : Google Scholar : PubMed/NCBI

65 

He L and Hannon GJ: MicroRNAs: Small RNAs with a big role in gene regulation. Nat Rev Genet. 5:522–531. 2004. View Article : Google Scholar : PubMed/NCBI

66 

Xiao C and Rajewsky K: MicroRNA control in the immune system: Basic principles. Cell. 136:26–36. 2009. View Article : Google Scholar : PubMed/NCBI

67 

Libânio D, Dinis-Ribeiro M and Pimentel-Nunes P: Helicobacter pylori and microRNAs: Relation with innate immunity and progression of preneoplastic conditions. World J Clin Oncol. 6:111–132. 2015. View Article : Google Scholar : PubMed/NCBI

68 

Noto JM and Peek RM: The role of microRNAs in Helicobacter pylori pathogenesis and gastric carcinogenesis. Front Cell Infect Microbiol. 1:212012. View Article : Google Scholar : PubMed/NCBI

69 

Matsushima K, Isomoto H, Inoue N, Nakayama T, Hayashi T, Nakayama M, Nakao K, Hirayama T and Kohno S: MicroRNA signatures in Helicobacter pylori-infected gastric mucosa. Int J Cancer. 128:361–370. 2011. View Article : Google Scholar : PubMed/NCBI

70 

Zhu Y, Jiang Q, Lou X, Ji X, Wen Z, Wu J, Tao H, Jiang T, He W, Wang C, et al: MicroRNAs up-regulated by CagA of Helicobacter pylori induce intestinal metaplasia of gastric epithelial cells. PLoS One. 7:e351472012. View Article : Google Scholar : PubMed/NCBI

71 

Feng Y, Wang L, Zeng J, Shen L, Liang X, Yu H, Liu S, Liu Z, Sun Y, Li W, et al: FoxM1 is overexpressed in Helicobacter pylori-induced gastric carcinogenesis and is negatively regulated by miR-370. Mol Cancer Res. 11:834–844. 2013. View Article : Google Scholar : PubMed/NCBI

72 

Li N, Tang B, Zhu ED, Li BS, Zhuang Y, Yu S, Lu DS, Zou QM, Xiao B and Mao XH: Increased miR-222 in H. pylori-associated gastric cancer correlated with tumor progression by promoting cancer cell proliferation and targeting RECK. FEBS Lett. 586:722–728. 2012. View Article : Google Scholar : PubMed/NCBI

73 

Belair C, Baud J, Chabas S, Sharma CM, Vogel J, Staedel C and Darfeuille F: Helicobacter pylori interferes with an embryonic stem cell micro RNA cluster to block cell cycle progression. Silence. 2:72011. View Article : Google Scholar : PubMed/NCBI

74 

Cheng SF, Li L and Wang LM: miR-155 and miR-146b negatively regulates IL6 in Helicobacter pylori (cagA+) infected gastroduodenal ulcer. Eur Rev Med Pharmacol Sci. 19:607–613. 2015.PubMed/NCBI

75 

Harr JC, Gonzalez-Sandoval A and Gasser SM: Histones and histone modifications in perinuclear chromatin anchoring: From yeast to man. EMBO Rep. 17:139–155. 2016. View Article : Google Scholar : PubMed/NCBI

76 

Schones DE, Cui K, Cuddapah S, Roh TY, Barski A, Wang Z, Wei G and Zhao K: Dynamic regulation of nucleosome positioning in the human genome. Cell. 132:887–898. 2008. View Article : Google Scholar : PubMed/NCBI

77 

Xia G, Schneider-Stock R, Diestel A, Habold C, Krueger S, Roessner A, Naumann M and Lendeckel U: Helicobacter pylori regulates p21 (WAF1) by histone H4 acetylation. Biochem Biophys Res Commun. 369:526–531. 2008. View Article : Google Scholar : PubMed/NCBI

78 

Fehri LF, Rechner C, Janssen S, Mak TN, Holland C, Bartfeld S, Brüggemann H and Meyer TF: Helicobacter pylori-induced modification of the histone H3 phosphorylation status in gastric epithelial cells reflects its impact on cell cycle regulation. Epigenetics. 4:577–586. 2009. View Article : Google Scholar : PubMed/NCBI

79 

Liang X, Zeng J, Wang L, Shen L, Li S, Ma L, Ci X, Yu J, Jia M, Sun Y, et al: Histone demethylase RBP2 induced by Helicobactor pylori CagA participates in the malignant transformation of gastric epithelial cells. Oncotarget. 5:5798–5807. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Chen S, Zhang R and Duan G: Pathogenic mechanisms of the oncoprotein CagA in H. pylori-induced gastric cancer (Review). Oncol Rep 36: 3087-3094, 2016.
APA
Chen, S., Zhang, R., & Duan, G. (2016). Pathogenic mechanisms of the oncoprotein CagA in H. pylori-induced gastric cancer (Review). Oncology Reports, 36, 3087-3094. https://doi.org/10.3892/or.2016.5145
MLA
Chen, S., Zhang, R., Duan, G."Pathogenic mechanisms of the oncoprotein CagA in H. pylori-induced gastric cancer (Review)". Oncology Reports 36.6 (2016): 3087-3094.
Chicago
Chen, S., Zhang, R., Duan, G."Pathogenic mechanisms of the oncoprotein CagA in H. pylori-induced gastric cancer (Review)". Oncology Reports 36, no. 6 (2016): 3087-3094. https://doi.org/10.3892/or.2016.5145
Copy and paste a formatted citation
x
Spandidos Publications style
Chen S, Zhang R and Duan G: Pathogenic mechanisms of the oncoprotein CagA in H. pylori-induced gastric cancer (Review). Oncol Rep 36: 3087-3094, 2016.
APA
Chen, S., Zhang, R., & Duan, G. (2016). Pathogenic mechanisms of the oncoprotein CagA in H. pylori-induced gastric cancer (Review). Oncology Reports, 36, 3087-3094. https://doi.org/10.3892/or.2016.5145
MLA
Chen, S., Zhang, R., Duan, G."Pathogenic mechanisms of the oncoprotein CagA in H. pylori-induced gastric cancer (Review)". Oncology Reports 36.6 (2016): 3087-3094.
Chicago
Chen, S., Zhang, R., Duan, G."Pathogenic mechanisms of the oncoprotein CagA in H. pylori-induced gastric cancer (Review)". Oncology Reports 36, no. 6 (2016): 3087-3094. https://doi.org/10.3892/or.2016.5145
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team