| RRC ID |
45295
|
| Author |
Otsuki T, Fujimoto D, Hirono Y, Goi T, Yamaguchi A.
|
| Title |
Thrombin conducts epithelial‑mesenchymal transition via protease‑activated receptor‑1 in human gastric cancer.
|
| Journal |
Int J Oncol
|
| Abstract |
Epithelial-mesenchymal transition (EMT) is thought to be a key step for cancer metastasis. Using an immunohistochemical approach with gastric carcinoma tissue, we found the expression of protease-activated receptor-1 (PAR1), along with a metalloproteinase known to activate PAR1, were associated with poorer prognosis, compared with expression-negative tumors, and activated PAR1 promotes gastric cancer cell invasion and proliferation in vivo. In this study we observed EMT induction by the PAR1 agonist α-thrombin, in human gastric cell lines stably expressing PAR1. We investigated α-thrombin-induced changes in the cell forms of pcDNA3.1-MKN45 (MKN45/Mock), pcDNA3.1‑PAR1 transfected MKN45 (MKN45/PAR1), and MKN74. Expression levels of epithelial and mesenchymal markers as well as the distribution of transcriptional factors of E-cadherin in the cytoplasm and nucleus were also noted in these cell lines. We observed α-thrombin-induced morphological changes in MKN45/PAR1 and MKN74 cells. Western blotting and immunohistochemistry of these cells indicated a fall in the expression level of E-cadherin and an increase in fibronectin expression after 48 h. PAR1 activation also induced significant increases in nuclear levels of the Snail which is a repressor of E-cadherin gene expression. We found EMT in gastric cancer cell lines that underwent α-thrombin-induced PAR1 activation.
|
| Volume |
45(6)
|
| Pages |
2287-94
|
| Published |
2014-12-1
|
| DOI |
10.3892/ijo.2014.2651
|
| PMID |
25231630
|
| MeSH |
Cadherins / biosynthesis
Cell Line, Tumor
Epithelial-Mesenchymal Transition / genetics*
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Neoplasm Invasiveness / genetics
Neoplasm Metastasis
Receptor, PAR-1 / biosynthesis*
Receptor, PAR-1 / genetics
Stomach Neoplasms / genetics*
Stomach Neoplasms / pathology
Thrombin / biosynthesis
Thrombin / genetics*
|
| IF |
3.899
|
| Times Cited |
13
|
|
WOS Category
|
ONCOLOGY
|
| Resource |
| Human and Animal Cells |
MKN45(RCB1001)
MKN74(RCB1002) |
