Downregulation of PAK5 inhibits glioma cell migration and invasion potentially through the PAK5-Egr1-MMP2 signaling pathway
Downregulation of PAK5 inhibits glioma cell migration and invasion potentially through the PAK5-Egr1-MMP2 signaling pathway
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DOI：
10.1007/s10014-013-0161-1
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发表时间：
2014-10-01
影响因子：
3.3
通讯作者：
Zheng, Jun-Nian
中科院分区：
文献类型：
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作者：
Han, Zheng-Xiang;Wang, Xiao-Xia;Zheng, Jun-Nian
PAK 5（p21活化激酶5）在人结肠直肠癌细胞中上调，并且是结肠癌发生中已知的肿瘤促进剂。关于PAK 5下游靶点的机制知之甚少，并且缺乏关于其在胶质瘤中的生物学意义的信息。在这项研究中，我们研究了PAK 5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。通过细胞生长试验和细胞周期分析观察细胞增殖情况。进行流式细胞术分析以评估细胞凋亡，并进行体外划痕试验、细胞迁移试验和明胶酶谱法以检查细胞迁移。进行蛋白质印迹分析以检查细胞中的信号转导。我们证明了在胶质瘤细胞中抑制PAK 5显著抑制细胞迁移和侵袭。我们还观察到，PAK 5在人脑胶质瘤细胞系中的抑制由于G1期阻滞而抑制细胞生长。流式细胞术和Western blot分析表明PAK 5可抑制细胞凋亡。这些结果表明，PAK 5-Egr 1-MMP 2信号通路参与肿瘤的进展，并可能在癌症预防和治疗中发挥潜在作用。
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.