Downregulation of p21-activated kinase-1 inhibits the growth of gastric cancer cells involving cyclin B1
Downregulation of p21-activated kinase-1 inhibits the growth of gastric cancer cells involving cyclin B1
复制标题
p21激活激酶1的下调抑制与细胞周期蛋白B1有关的胃癌细胞的生长
DOI：
10.1002/ijc.24588
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发表时间：
2009-12-01
影响因子：
6.4
通讯作者：
Li, Feng
中科院分区：
文献类型：
--
作者：
Liu, Funan;Li, Xiaodong;Li, Feng
P21激活蛋白1(P21-Actiated Kinase 1，PAK1)是一种丝氨酸/苏氨酸激酶，与细胞骨架重塑、细胞运动、细胞凋亡和细胞转化有关。然而，Ak1在胃癌中的作用仍不清楚。本研究采用免疫印迹法检测了40例胃癌组织中pak1的表达。Ak1的过表达与胃癌的进展、转移和预后有关。此外，我们还发现，Ak1基因的表达下调显著抑制了胃癌细胞的锚定依赖性和非锚定依赖性生长，并显著抑制了胃癌细胞异种移植瘤的生长。进一步的研究表明，pak1可以在mRNA和蛋白水平上调控细胞周期蛋白B1的表达，并影响细胞周期蛋白B1的亚细胞分布和启动子活性。缺失和突变分析结果在Cyclin B1启动子-321位提供了一个新的核因子-kappa B结合位点，提示pak1可能通过核因子-kappa B调控胃癌细胞周期蛋白b1的转录。(C)2009年UICC
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-kappa B binding sites at position -321 of cyclin B1 promoter, and indicated that Pak1 regulated the transcription of cyclin B1 in gastric cancer through NF-kappa B. In conclusion, Pak1 may be a potential prognostic marker and therapeutic target in gastric cancer. (c) 2009 UICC