Institute of Life and Health Engineering and National Engineering and Research Center for Genetic Medicine, Jinan University, Guangzhou, P. R. China.
Proteomics. 2011 Sep;11(18):3657-64. doi: 10.1002/pmic.201100215. Epub 2011 Aug 2.
We previously used proteomics technology to globally identify gastric cancer-associated proteins and found that gastrokine 1 (GKN1) was dramatically underexpressed in gastric cancer tissues. Here, we further showed that GKN1 could inhibit cell growth and induce cell cycle arrest in gastric cancer cells. The activity of protein kinase PKCδ/θ was inhibited by GKN1, whereas the activity of ERK1/2 and JNK1/2 was increased by GKN1, suggesting that GKN1 induced growth inhibition of gastric cancer cells by synergistically regulating the activity of these protein kinases. Seventy-four proteins were found to be regulated by GKN1 by proteomics analysis, including α-enolase (ENO1) and Cathepsin D. Interestingly, ENO1 is an important hub in the protein-protein interaction network of the 74 differential proteins. Silencing of ENO1 resulted in growth inhibition and cell cycle arrest of gastric cancer cells, similar to the effect of GKN1 overexpression in cells, whereas ENO1 overexpression blocked GKN1-induced growth inhibition and cell cycle arrest. These observations suggested that ENO1 downregulation played an important role in GKN1-induced growth inhibition of gastric cancer cells.
我们先前使用蛋白质组学技术对胃癌相关蛋白进行了全面鉴定，发现胃动蛋白 1（GKN1）在胃癌组织中明显低表达。在这里，我们进一步表明 GKN1 可以抑制胃癌细胞的生长并诱导细胞周期停滞。GKN1 抑制蛋白激酶 PKCδ/θ 的活性，而 GKN1 增加 ERK1/2 和 JNK1/2 的活性，表明 GKN1 通过协同调节这些蛋白激酶的活性诱导胃癌细胞生长抑制。蛋白质组学分析发现 GKN1 可调节 74 种蛋白，包括α-烯醇化酶（ENO1）和组织蛋白酶 D。有趣的是，ENO1 是 74 种差异蛋白的蛋白质-蛋白质相互作用网络中的一个重要枢纽。沉默 ENO1 导致胃癌细胞生长抑制和细胞周期停滞，与细胞中 GKN1 过表达的效果相似，而 ENO1 过表达则阻断了 GKN1 诱导的生长抑制和细胞周期停滞。这些观察结果表明 ENO1 的下调在 GKN1 诱导的胃癌细胞生长抑制中发挥了重要作用。
