| RRC ID |
83718
|
| Author |
Kubo S, Ninomiya R, Kajiwara T, Tokunaga A, Matsuda S, Murakami K, Yamaoka Y, Aigaki T, Hamada F.
|
| Title |
Helicobacter pylori virulence factor CagA promotes Snail-mediated epithelial-mesenchymal transition and invasive behavior by downregulating Semaphorin 5A in gastric epithelial cells.
|
| Journal |
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.
|
| Volume |
750
|
| Pages |
151421
|
| Published |
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
|
| Resource |
| Drosophila |
|
