| RRC ID |
65745
|
| 著者 |
Sougleri IS, Papadakos KS, Zadik MP, Mavri-Vavagianni M, Mentis AF, Sgouras DN.
|
| タイトル |
Helicobacter pylori CagA protein induces factors involved in the epithelial to mesenchymal transition (EMT) in infected gastric epithelial cells in an EPIYA- phosphorylation-dependent manner.
|
| ジャーナル |
FEBS J
|
| Abstract |
As a result of Helicobacter pylori adhesion to gastric epithelial cells, the bacterial effector cytotoxin-associated gene A (CagA) is translocated intracellularly, and after hierarchical tyrosine phosphorylation on multiple EPIYA motifs, de-regulates cellular polarity and contributes to induction of an elongation and scattering phenotype that resembles the epithelial to mesenchymal transition (EMT). Stromelysin-1/matrix metalloproteinase-3 (MMP-3) has been reported to induce a sequence of molecular alterations leading to stable EMT transition and carcinogenesis in epithelial cells. To identify the putative role of CagA protein in MMP-3 induction, we exploited an experimental H. pylori infection system in gastric epithelial cell lines. We utilized isogenic mutants expressing CagA protein with variable numbers of EPIYA and phosphorylation-deficient EPIFA motifs, as well as cagA knockout and translocation-deficient cagE knockout strains. Increased levels of MMP-3 transcriptional activation were demonstrated by quantitative real time-PCR for strains with more than two terminal EPIYA phosphorylation motifs in CagA. MMP-3 expression in total cell lysates and the corresponding culture supernatants was associated with CagA expression and translocation and was dependent on CagA phosphorylation. A CagA EPIYA phosphorylation-dependent increase in gelatinase and caseinolytic activity was also detected in culture supernatants by zymography. A significant increase in the transcriptional activity of the mesenchymal markers Vimentin, Snail and ZEB1 and the stem cell marker CD44 was observed in the case of CagA containing phosphorylation-functional EPIYA motifs. Our data suggest that CagA protein induces EMT through EPIYA phosphorylation-dependent up-regulation of MMP-3. Moreover, no significant increase in EMT and stem cell markers was observed following infection with H. pylori strains that cannot effectively translocate CagA protein.
|
| 巻・号 |
283(2)
|
| ページ |
206-20
|
| 公開日 |
2016-1-1
|
| DOI |
10.1111/febs.13592
|
| PMID |
26907789
|
| MeSH |
Amino Acid Motifs
Amino Acid Sequence
Animals
Antigens, Bacterial / genetics
Antigens, Bacterial / metabolism*
Bacterial Proteins / genetics
Bacterial Proteins / metabolism*
Cell Line, Tumor
Epithelial Cells / metabolism*
Epithelial Cells / microbiology
Epithelial-Mesenchymal Transition*
Gastric Mucosa / metabolism*
Gastric Mucosa / microbiology
Helicobacter Infections / metabolism*
Helicobacter Infections / pathology
Helicobacter pylori / pathogenicity*
Host-Pathogen Interactions
Humans
Hyaluronan Receptors / metabolism
Matrix Metalloproteinase 3 / metabolism
Molecular Sequence Data
Phosphorylation
Vimentin / metabolism
|
| IF |
4.392
|
| リソース情報 |
| ヒト・動物細胞 |
MKN45(RCB1001) |
