Calcyclin-binding protein inhibits proliferation, tumorigenicity, and invasion of gastric cancer

被引:64
作者
Ning, Xiaoxuan [1 ,2 ,3 ]
Sun, Shiren [1 ,2 ,5 ]
Hong, Liu [1 ,2 ]
Liang, Jie [1 ,2 ]
Liu, Lili [1 ,2 ]
Han, Shuang [1 ,2 ]
Liu, Zhiguo [1 ,2 ]
Shi, Yongquan [1 ,2 ]
Li, Yuan
Gong, Weiqin [3 ]
Zhang, Shanhong [3 ]
Chen, Yu [1 ,2 ]
Guo, Xueyan [1 ,2 ]
Cheng, Yi [4 ]
Wu, Kaichun [1 ,2 ]
Fan, Daiming [1 ,2 ]
机构
[1] Fourth Mil Med Univ, Inst Digest Dis, Xijing Hosp, Xian 710032, Shaanxi Prov, Peoples R China
[2] Fourth Mil Med Univ, Xijing Hosp, State Key Lab Canc Biol, Xian 710032, Shaanxi Prov, Peoples R China
[3] Fourth Mil Med Univ, Xijing Hosp, Dept Geriatr, Xian 710032, Shaanxi Prov, Peoples R China
[4] Wuhan Gen Hosp Guangzhou Command, Dept Gastroenterol, Wuhan, Hubei, Peoples R China
[5] Fourth Mil Med Univ, Dept Nephrol, Xijing Hosp, Xian 710032, Shaanxi Prov, Peoples R China
关键词
D O I
10.1158/1541-7786.MCR-06-0426
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP), a target protein of the S100 family, which includes S100A6, S100A1, S100A12, S100B, and S100P has been identified as a component of a novel ubiquitinylation complex leading to beta-catenin degradation. However, the function of CacyBP/SIP in gastric cancer has not been elucidated. In the present study, we prepared CacyBP/SIP overexpressing and knockdown cell lines of gastric cancer. Forced CacyBP/SIP expression inhibited the proliferation of gastric cancer cells, suppressed tumorigenicity in vitro, and prolonged the survival time of tumor-bearing nude mice. In addition, increased CacyBP/SIP repressed the invasive potential of gastric cancer cells. Conversely, the down-regulation of CacyBP/SIP by RNA interference showed the opposite effects. Further studies showed that depressed CacyBP/SIP increased the expression of total and nuclear beta-catenin at the protein level and elevated the transcriptional activity of Tcf/LEF. Taken together, our results suggest that CacyBP/SIP may be a potential inhibitor of cell growth and invasion in the gastric cancer cell, at least in part through the effect on beta-catenin protein expression and transcriptional activation of Tcf/LEF.
引用
收藏
页码:1254 / 1262
页数:9
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