EPAC1 overexpression is a prognostic marker and its inhibition shows promising therapeutic potential for gastric cancer.
EPAC1 overexpression is a prognostic marker and its inhibition shows promising therapeutic potential for gastric cancer.
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DOI：
10.3892/or.2017.5442
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发表时间：
2017-04
期刊：
影响因子：
4.2
通讯作者：
Lin KY
中科院分区：
文献类型：
--
作者：
Sun DP;Fang CL;Chen HK;Wen KS;Hseu YC;Hung ST;Uen YH;Lin KY
cAMP 信号传导控制多种细胞功能。除了众所周知的信号转导器 cAMP 依赖性蛋白激酶外，最近发现的转导器是由 cAMP 直接激活的交换蛋白 (EPAC)。 EPAC 反应由小 G 蛋白介导，可调节细胞粘附、迁移和增殖等生物功能。最近，EPAC1的临床重要性受到越来越多的关注。本研究探讨了EPAC1的表达与胃癌（GC）患者的各种临床病理参数以及生存率之间的相关性。本研究的患者队列由 1999 年至 2011 年出现的 141 例 GC 病例组成；所有病例均可获得记录的临床病理参数和临床结果。采用免疫印迹、免疫组织化学和实时定量PCR检测胃细胞和组织中EPAC1的表达。采用siRNA技术研究EPAC1敲低对细胞增殖和侵袭的影响。在 GC 细胞和组织中发现 EPAC1 表达增加。 EPAC1的过表达与侵袭深度（P=0.0021）、分期（P=0.0429）和血管侵犯（P=0.0049）相关，并且与较差的无病生存（P=0.0029）和总生存（P=0.0024）相关。单变量Cox回归分析显示EPAC1的过度表达是GC的预后标志物（P=0.038）。此外，细胞研究表明，GC 细胞中 EPAC1 的敲低可抑制细胞增殖和侵袭。 EPAC1的过度表达可以作为预测GC患者预后的标志物，EPAC1代表了治疗GC的潜在治疗方式。
cAMP signaling controls a variety of cellular functions. In addition to the well-known signal transducer cAMP-dependent protein kinase, a more recently discovered transducer is the exchange protein directly activated by cAMP (EPAC). EPAC responses are mediated by small G proteins, which regulate biologic functions such as cell adhesion, migration and proliferation. Recently, the clinical importance of EPAC1 has received increased attention. This study investigated the correlations between the expression of EPAC1 and various clinicopathologic parameters as well as the survival of the patients with gastric cancer (GC). The patient cohort in this study consisted of 141 cases of GC that presented from 1999 through 2011; documented clinicopathologic parameters and clinical outcomes were available for all cases. Immunoblotting, immunohistochemistry and quantitative real-time PCR were used to examine EPAC1 expression in gastric cells and tissues. siRNA technology was used to study the effect of EPAC1 knockdown on cell proliferation and invasion. An increase in EPAC1 expression was found in GC cells and tissues. The overexpression of EPAC1 was associated with the depth of invasion (P=0.0021), stage (P=0.0429), and vascular invasion (P=0.0049) and was correlated with poor disease-free survival (P=0.0029) and overall survival (P=0.0024). A univariate Cox regression analysis showed that the overexpression of EPAC1 was a prognostic marker for GC (P=0.038). Furthermore, cell studies indicated that the knockdown of EPAC1 in GC cells suppressed cell proliferation and invasion. The overexpression of EPAC1 can be used as a marker to predict the outcome of patients with GC, and EPAC1 represents a potential therapeutic modality for treating GC.