論文 - 詳細
| RRC ID | 44917 |
|---|---|
| 著者 | Dong Z, Fu S, Xu X, Yang Y, Du L, Li W, Kan S, Li Z, Zhang X, Wang L, Li J, Liu H, Qu X, Wang C. |
| タイトル | Leptin-mediated regulation of ICAM-1 is Rho/ROCK dependent and enhances gastric cancer cell migration. |
| ジャーナル | Br J Cancer |
| Abstract |
BACKGROUND:Our previous study indicates that leptin enhances gastric cancer (GC) invasion. However, the exact effect of leptin on GC metastasis and its underlying mechanism remain unclear. Intercellular adhesion molecule-1 (ICAM-1), a major molecule in stabilising cell-cell and cell-extracellular matrix interactions, is overexpressed and has crucial roles in tumour metastasis. METHODS:Here, we investigated leptin and ICAM-1 expression in GC tissues. Furthermore, we characterised the influence of leptin on ICAM-1 expression in GC cells and elucidated the underlying mechanism. RESULTS:Leptin and ICAM-1 were overexpressed in GC tissues, and a strong positive correlation was observed. They were also related with clinical stage or lymph node metastasis. Furthermore, leptin induced GC cell (AGS and MKN-45) migration by upregulating ICAM-1, and knockdown of ICAM-1 by small interference RNA (siRNA) blocked this process. Cell surface ICAM-1, as well as soluble ICAM-1 (sICAM-1), was also enhanced by leptin. Moreover, leptin increased ICAM-1 expression through Rho/ROCK pathway, which was attenuated by pharmacological inhibition of Rho (C3 transferase) or its downstream effector kinase Rho-associated protein kinase (ROCK) (Y-27632). CONCLUSIONS:Our findings indicate that leptin enhances GC cell migration by increasing ICAM-1 through Rho/ROCK pathway, which might provide new insight into the significance of leptin in GC. |
| 巻・号 | 110(7) |
| ページ | 1801-10 |
| 公開日 | 2014-4-2 |
| DOI | 10.1038/bjc.2014.70 |
| PII | bjc201470 |
| PMID | 24548863 |
| PMC | PMC3974087 |
| MeSH | Adult Aged Cell Movement* / drug effects Cell Movement* / genetics Female Gene Expression Regulation, Neoplastic / drug effects Humans Intercellular Adhesion Molecule-1 / genetics* Leptin / metabolism* Male Middle Aged Signal Transduction / drug effects Signal Transduction / genetics Stomach Neoplasms / genetics Stomach Neoplasms / pathology* Tumor Cells, Cultured rho GTP-Binding Proteins / physiology* rho-Associated Kinases / physiology* |
| IF | 5.791 |
| 引用数 | 28 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | MKN45(RCB1001) |