RRC ID 83718
著者 Kubo S, Ninomiya R, Kajiwara T, Tokunaga A, Matsuda S, Murakami K, Yamaoka Y, Aigaki T, Hamada F.
タイトル Helicobacter pylori virulence factor CagA promotes Snail-mediated epithelial-mesenchymal transition and invasive behavior by downregulating Semaphorin 5A in gastric epithelial cells.
ジャーナル Biochem Biophys Res Commun
Abstract Helicobacter pylori (H. pylori) infection is one of the major risk factors of stomach cancer. Strains carrying the oncogenic cytotoxin CagA (cytotoxin-associated gene A) induce epithelial-mesenchymal transition (EMT) and contribute to tumor progression and metastasis. However, the mechanism in which CagA induces EMT has not been defined. In this study, using genetic methods in Drosophila, we identified Semaphorin 5A (SEMA5A) as a new target for CagA. We showed that infection with CagA-positive H. pylori downregulated the expression level of SEMA5A to induce expression of EMT-driving transcription factor Snail and mesenchymal marker N-cadherin, and promote invasive behavior in gastric epithelial cells. Furthermore, we demonstrated that transient over-expression of SEMA5A in H. pylori-infected cells inhibited CagA-mediated gain of mesenchymal phenotype. These results suggest that SEMA5A could be a key mediator of EMT and gastric carcinogenesis caused by CagA-positive H. pylori infection.
巻・号 750
ページ 151421
公開日 2025-3-1
DOI 10.1016/j.bbrc.2025.151421
PII S0006-291X(25)00135-4
PMID 39892055
MeSH Animals Antigens, Bacterial* / genetics Antigens, Bacterial* / metabolism Bacterial Proteins* / genetics Bacterial Proteins* / metabolism Down-Regulation* Epithelial Cells / metabolism Epithelial Cells / microbiology Epithelial Cells / pathology Epithelial-Mesenchymal Transition* Gastric Mucosa / metabolism Gastric Mucosa / microbiology Gastric Mucosa / pathology Helicobacter Infections / metabolism Helicobacter Infections / microbiology Helicobacter Infections / pathology Helicobacter pylori* / metabolism Helicobacter pylori* / pathogenicity Humans Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism Semaphorins* / genetics Semaphorins* / metabolism Snail Family Transcription Factors* / genetics Snail Family Transcription Factors* / metabolism Stomach Neoplasms / metabolism Stomach Neoplasms / microbiology Stomach Neoplasms / pathology Virulence Factors / genetics Virulence Factors / metabolism
IF 2.985
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