| RRC ID |
62893
|
| 著者 |
Tiffon C, Giraud J, Molina-Castro SE, Peru S, Seeneevassen L, Sifré E, Staedel C, Bessède E, Dubus P, Mégraud F, Lehours P, Martin OCB, Varon C.
|
| タイトル |
TAZ Controls Helicobacter pylori-Induced Epithelial-Mesenchymal Transition and Cancer Stem Cell-Like Invasive and Tumorigenic Properties.
|
| ジャーナル |
Cells
|
| Abstract |
Helicobacter pylori infection, the main risk factor for gastric cancer (GC), leads to an epithelial-mesenchymal transition (EMT) of gastric epithelium contributing to gastric cancer stem cell (CSC) emergence. The Hippo pathway effectors yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ) control cancer initiation and progression in many cancers including GC. Here, we investigated the role of TAZ in the early steps of H. pylori-mediated gastric carcinogenesis. TAZ implication in EMT, invasion, and CSC-related tumorigenic properties were evaluated in three gastric epithelial cell lines infected by H. pylori. We showed that H. pylori infection increased TAZ nuclear expression and transcriptional enhancer TEA domain (TEAD) transcription factors transcriptional activity. Nuclear TAZ and zinc finger E-box-binding homeobox 1 (ZEB1) were co-overexpressed in cells harboring a mesenchymal phenotype in vitro, and in areas of regenerative hyperplasia in gastric mucosa of H. pylori-infected patients and experimentally infected mice, as well as at the invasive front of gastric carcinoma. TAZ silencing reduced ZEB1 expression and EMT phenotype, and strongly inhibited invasion and tumorsphere formation induced by H. pylori. In conclusion, TAZ activation in response to H. pylori infection contributes to H. pylori-induced EMT, invasion, and CSC-like tumorigenic properties. TAZ overexpression in H. pylori-induced pre-neoplastic lesions and in GC could therefore constitute a biomarker of early transformation in gastric carcinogenesis.
|
| 巻・号 |
9(6)
|
| 公開日 |
2020-6-13
|
| DOI |
10.3390/cells9061462
|
| PII |
cells9061462
|
| PMID |
32545795
|
| PMC |
PMC7348942
|
| MeSH |
Animals
Epithelial Cells / metabolism*
Epithelial Cells / pathology
Epithelial-Mesenchymal Transition / physiology
Gastric Mucosa / pathology*
Helicobacter Infections / genetics
Helicobacter Infections / metabolism*
Helicobacter Infections / pathology
Helicobacter pylori / metabolism
Humans
Hyaluronan Receptors / metabolism
Mice
Neoplastic Stem Cells / metabolism
Neoplastic Stem Cells / pathology*
Transcription Factors / metabolism
|
| IF |
4.366
|
| リソース情報 |
| ヒト・動物細胞 |
MKN45(RCB1001) |
