Leptin-mediated regulation of ICAM-1 is Rho/ROCK dependent and enhances gastric cancer cell migration

被引:45
作者
Dong, Z. [1 ]
Fu, S. [1 ]
Xu, X. [2 ]
Yang, Y. [1 ]
Du, L. [1 ]
Li, W. [1 ]
Kan, S. [1 ]
Li, Z. [1 ]
Zhang, X. [1 ]
Wang, L. [1 ]
Li, J. [1 ]
Liu, H. [1 ]
Qu, X. [3 ]
Wang, C. [1 ]
机构
[1] Shandong Univ, Qilu Hosp, Dept Clin Lab, Jinan 250012, Shandong, Peoples R China
[2] Shandong Univ, Qilu Hosp, Dept Obstet & Gynecol, Jinan 250012, Shandong, Peoples R China
[3] Shandong Univ, Qilu Hosp, Inst Basic Med Sci, Jinan 250012, Shandong, Peoples R China
基金
高等学校博士学科点专项科研基金;
关键词
gastric cancer; leptin; ICAM-1; Rho/ROCK; migration; INTERCELLULAR-ADHESION MOLECULE-1; CLINICAL-SIGNIFICANCE; HELICOBACTER-PYLORI; KINASE PATHWAY; UP-REGULATION; SERUM-LEVELS; LUNG-CANCER; RHO-GTPASES; EXPRESSION; RECEPTOR;
D O I
10.1038/bjc.2014.70
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1801 / 1810
页数:10
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