RRC ID 45295
著者 Otsuki T, Fujimoto D, Hirono Y, Goi T, Yamaguchi A.
タイトル Thrombin conducts epithelial‑mesenchymal transition via protease‑activated receptor‑1 in human gastric cancer.
ジャーナル 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.
巻・号 45(6)
ページ 2287-94
公開日 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
引用数 13
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 MKN45(RCB1001) MKN74(RCB1002)