Liu Funan, Li Xiaodong, Wang Chunyu, Cai Xinze, Du Zhongmin, Xu Huimian, Li Feng
Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, [corrected] China Medical University, Shenyang, Liaoning, People's Republic of China.
Int J Cancer. 2009 Dec 1;125(11):2511-9. doi: 10.1002/ijc.24588.
p21-Activated kinase 1 (Pak1), a serine/threonine kinase, has been implicated in cytoskeletal remodelling, cell motility, apoptosis and transformation. However, the role of Pak1 in gastric cancer remains unclear. In this study, we detected Pak1 expression in gastric cancer tissues from 40 patients by western blot. Overexpression of Pak1 was associated with progression, metastasis and prognosis of gastric cancer. In addition, we found that knockdown of Pak1 expression significantly inhibited anchorage-dependent and anchorage-independent growth in gastric cancer cells, and markedly inhibited gastric cancer cell xenograft tumor growth. In further study, data showed that Pak1 could regulate the expression of cyclin B1 at the mRNA and protein levels, and impact the subcellular distribution and the promoter activity of cyclin B1. Results from deletion and mutant analysis supplied a new NF-kappaB binding sites at position -321 of cyclin B1 promoter, and indicated that Pak1 regulated the transcription of cyclin B1 in gastric cancer through NF-kappaB. In conclusion, Pak1 may be a potential prognostic marker and therapeutic target in gastric cancer.
p21激活激酶1（Pak1）是一种丝氨酸/苏氨酸激酶，与细胞骨架重塑、细胞运动、细胞凋亡及细胞转化有关。然而，Pak1在胃癌中的作用仍不清楚。在本研究中，我们通过蛋白质印迹法检测了40例胃癌组织中Pak1的表达。Pak1的过表达与胃癌的进展、转移及预后相关。此外，我们发现敲低Pak1表达可显著抑制胃癌细胞的贴壁依赖性和非贴壁依赖性生长，并明显抑制胃癌细胞异种移植瘤的生长。在进一步研究中，数据显示Pak1可在mRNA和蛋白质水平调节细胞周期蛋白B1的表达，并影响细胞周期蛋白B1的亚细胞分布及启动子活性。缺失和突变分析结果在细胞周期蛋白B1启动子的-321位提供了一个新的核因子κB结合位点，并表明Pak1在胃癌中通过核因子κB调节细胞周期蛋白B1的转录。总之，Pak1可能是胃癌潜在的预后标志物和治疗靶点。
