Calcyclin-binding protein inhibits proliferation, tumorigenicity, and invasion of gastric cancer
Calcyclin-binding protein inhibits proliferation, tumorigenicity, and invasion of gastric cancer
复制标题
钙周期蛋白结合蛋白抑制胃癌的增殖、致瘤性和侵袭。
DOI：
10.1158/1541-7786.mcr-06-0426
复制
发表时间：
2007-12-01
影响因子：
5.2
通讯作者：
Fan, Daiming
中科院分区：
文献类型：
--
作者：
Ning, Xiaoxuan;Sun, Shiren;Fan, Daiming
钙周期蛋白结合蛋白/Siah-1相互作用蛋白(CacyBP/SIP)是S100家族的靶蛋白，包括S100A6、S100A1、S100A12、S100B和S100P，是导致β-连环蛋白降解的泛素化复合体的一种成分。然而，CacyBP/SIP在胃癌中的作用尚不清楚。在本研究中，我们建立了CacyBP/SIP过表达和基因敲除的胃癌细胞系。强制表达CacyBP/SIP可抑制胃癌细胞的增殖，抑制体外致瘤性，延长荷瘤裸鼠的生存时间。此外，CacyBP/SIP的增加抑制了胃癌细胞的侵袭潜能。反之，RNA干扰下调CacyBP/SIP则表现出相反的作用。进一步的研究表明，抑制CacyBP/SIP后，总的和核的β-连环素在蛋白水平上的表达增加，Tcf/Lef的转录活性增强。综上所述，我们的结果提示，CacyBP/SIP可能是一种潜在的抑制胃癌细胞生长和侵袭的基因，至少部分是通过影响β-连环蛋白的表达和Tcf/Lef的转录激活来实现的。
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.