Differential oncogenic potential of geographically distinct <i>Helicobacter pylori</i> CagA isoforms in mice

Miura, Motohiro; Ohnishi, Naomi; Tanaka, Shinya; Yanagiya, Kohei; Hatakeyama, Masanori

doi:10.1002/ijc.24740

Cited by 66 publications

(56 citation statements)

References 71 publications

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“…The above observations support the hypothesis that specific TPM patterns could determine the carcinogenic potential of H. pylori isolates, and partly explaining the geographic differences in GC incidence (1). In fact, very recently CagA have been recognized as the first bacterial oncoprotein which acts in mammalian cells (19) and its carcinogenic activity is modulated by specific TPM patterns (20). Therefore, accurate detection of the EPIYA pattern may become a useful prognostic tool for gastric malignancy due to H. pylori infection.…”

supporting

confidence: 66%

EPIYA motif patterns among Cuban Helicobacter pylori CagA positive strains

Torres¹,

González²,

Melián³

et al. 2011

biomedica

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supporting

confidence: 66%

EPIYA motif patterns among Cuban Helicobacter pylori CagA positive strains

Torres¹,

González²,

Melián³

et al. 2011

biomedica

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“…pylori strains exhibits a higher oncogenic potential than from western strains, which was attributed to the highly polymorphic EPIYA sequences in the C-terminal region. [38][39][40] From our point of view, the discovery of the CagA 1-200 membrane-binding domain with its inhibitory effect on CagA-induced host cell signaling will add to our understanding of CagA's role as a bacterial protein and of H. pylori induced gastric diseases.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Purpose of recently detected inhibitory domain of theHelicobacter pyloriprotein CagA

Steininger

Pelz²,

Vogelmann³

2011

Gut Microbes

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H elicobacter pylori infection is the most common bacterial infection worldwide and is strongly associated with gastric oncogenesis. Recently, we discovered that the H. pylori protein CagA, a risk factor for carcinogenesis, consists of two distinct membranetargeting domains. The C-terminal membrane-binding domain induces host cell responses associated with a high oncogenic potential. The N-terminal membrane-targeting domain, however, localizes to a different membrane substructure at the site of newly formed cellcell contacts thereby diminishing the effects of C-terminal signaling motifs on host cell physiology. This inhibitory function may allow H. pylori to establish a colonization niche in the host by maintaining the host epithelial architecture and thus decreasing the oncogenic potential as a side effect. From a bacterial standpoint, however, its main purpose maybe is to translocate the CagA protein via the type IV secretion apparatus into host epithelial cells.

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“…Many of the alterations caused by CagA are associated with malignant transformation of cells (2, 8, 11, 27-29, 33, 49, 54, 56). CagA expression in a transgenic mouse model leads to the development of tumors, and CagA is required for H. pylori-induced gastric carcinoma in a Mongolian gerbil model (23,38,43). Therefore, CagA is considered to be a bacterial oncoprotein (26).…”

mentioning

confidence: 99%

“…1) (27,28,30). Several studies have shown that H. pylori strains with an East Asian form of CagA (EPIYA-D) are associated with an increased risk of gastric cancer compared to strains with a Western form of CagA (EPIYA-C) (3,6,30,32,38,40).…”

mentioning

confidence: 99%

J-Western Forms of Helicobacter pylori cagA Constitute a Distinct Phylogenetic Group with a Widespread Geographic Distribution

et al. 2012

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Chronic infection with Helicobacter pylori strains expressing the bacterial oncoprotein CagA confers an increased risk of gastric cancer. While much is known about the ancestry and molecular evolution of Western, East Asian, and Amerindian cagA sequences, relatively little is understood about a fourth group, known as "J-Western," which has been detected mainly in strains from Okinawa, Japan. We show here that J-Western cagA sequences have a more widespread global distribution than previously recognized, occur in strains with multiple different ancestral origins (based on multilocus sequence typing [MLST] analysis), and did not arise recently. As shown by comparisons of Western and J-Western forms of CagA, there are 45 fixed or nearly fixed amino acid differences, and J-Western forms contain a unique 4-amino-acid insertion. The mean nucleotide diversity of synonymous sites ( s ) is slightly lower in the J-Western group than in the Western and East Asian groups (0.066, 0.086, and 0.083, respectively), which suggests that the three groups have comparable, but not equivalent, effective population sizes. The reduced s of the J-Western group is attributable to ancestral recombination events within the 5= region of cagA. Population genetic analyses suggest that within the cagA region encoding EPIYA motifs, the East Asian group underwent a marked reduction in effective population size compared to the Western and J-Western groups, in association with positive selection. Finally, we show that J-Western cagA sequences are found mainly in strains producing m2 forms of the secreted VacA toxin and propose that these functionally interacting proteins coevolved to optimize the gastric colonization capacity of H. pylori.

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Differential oncogenic potential of geographically distinct Helicobacter pylori CagA isoforms in mice

Cited by 66 publications

References 71 publications

EPIYA motif patterns among Cuban Helicobacter pylori CagA positive strains

EPIYA motif patterns among Cuban Helicobacter pylori CagA positive strains

Purpose of recently detected inhibitory domain of theHelicobacter pyloriprotein CagA

J-Western Forms of Helicobacter pylori cagA Constitute a Distinct Phylogenetic Group with a Widespread Geographic Distribution

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