Han Zheng-Xiang, Wang Xiao-Xia, Zhang Shang-Nuan, Wu Jin-Xia, Qian He-ya, Wen Yi-yang, Tian Hui, Pei Dong-Sheng, Zheng Jun-Nian
Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, China.
Brain Tumor Pathol. 2014 Oct;31(4):234-41. doi: 10.1007/s10014-013-0161-1. Epub 2013 Sep 6.
PAK5 (p21 activated kinase 5) is upregulated in human colorectal carcinoma cells and is a known tumor promoter in carcinogenesis of the colon. Little is known regarding the mechanisms underlying the downstream targets of PAK5, and information concerning its biological significance in glioma is lacking. In this study, we investigated the effects of PAK5 on proliferation, migration, invasion, and apoptosis in human U87 and U251 glioma cells and examined the underlying molecular mechanism. We performed cell growth assays and cell cycle analysis to observe the cell proliferation. Flow cytometry analysis was performed to evaluate apoptosis, and in vitro scratch assays, cell migration assays, and gelatin zymography were performed to examine cell migration. Western blot analysis was performed to examine signal transduction in the cells. We demonstrated that suppression of PAK5 in glioma cells significantly inhibited cell migration and invasion. We also observed that suppression of PAK5 in human glioma cell lines inhibited cell growth because of G1 phase arrest. Additionally, flow cytometry and Western blot analysis indicated that PAK5 could inhibit cell apoptosis. These results suggest that the PAK5-Egr1-MMP2 signaling pathway is involved in tumor progression and may have a potential role in cancer prevention and treatment.
PAK5（p21激活激酶5）在人结肠癌细胞中上调，是结肠癌发生过程中已知的肿瘤促进因子。关于PAK5下游靶点的潜在机制知之甚少，且缺乏其在胶质瘤中生物学意义的相关信息。在本研究中，我们调查了PAK5对人U87和U251胶质瘤细胞增殖、迁移、侵袭和凋亡的影响，并研究了潜在的分子机制。我们进行了细胞生长试验和细胞周期分析以观察细胞增殖。进行流式细胞术分析以评估凋亡，并进行体外划痕试验、细胞迁移试验和明胶酶谱分析以检测细胞迁移。进行蛋白质免疫印迹分析以检测细胞中的信号转导。我们证明，抑制胶质瘤细胞中的PAK5可显著抑制细胞迁移和侵袭。我们还观察到，抑制人胶质瘤细胞系中的PAK5会因G期阻滞而抑制细胞生长。此外，流式细胞术和蛋白质免疫印迹分析表明，PAK5可抑制细胞凋亡。这些结果表明，PAK5-Egr1-MMP2信号通路参与肿瘤进展，可能在癌症预防和治疗中具有潜在作用。 1
