p27Kip1 Promotes Migration of Metastatic Hepatocellular Carcinoma Cells
p27Kip1 Promotes Migration of Metastatic Hepatocellular Carcinoma Cells
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DOI：
10.1159/000152939
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发表时间：
2008-01-01
期刊：
影响因子：
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通讯作者：
Fan, Sheung Tat
中科院分区：
文献类型：
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作者：
Wang, Xiao Qi;Lui, Eric Lik Hang;Fan, Sheung Tat
背景/目的：p27（Kip 1）（p27）是细胞周期蛋白/细胞周期蛋白依赖性激酶抑制剂（CKIs）的Cip/Kip家族的成员，并且已经发现其关于细胞运动调节的CKI非依赖性功能。然而，p27是促进还是抑制细胞迁移存在争议。本研究探讨p27在转移性肝癌细胞中的迁移调节作用。方法：采用RNA干扰、RhoA-GTP pull-down实验、Western blot、免疫组化、transwell实验和创伤愈合实验。结果如下：高水平的p27和磷酸化p27（Ser 10）检测转移性肝癌细胞，MHCC 97 L和MHCC 97 H，与非转移性肝癌细胞，PLC和Hep 3B相比。我们假设p27负责HCC细胞中转移相关的迁移，并通过使用p27 RNA干扰方法来验证这一假设。当MHCC 97 L细胞中p27被敲低时，观察到RhoA活性增加，进一步导致应力纤维形成，并减少细胞迁移和伤口愈合。此外，转移性肝癌细胞的高p27和低stathmin表达表明，p27-stathmin相互作用的迁移抑制可能不是转移性肝癌细胞的主要调节途径。结论：p27通过调节RhoA活性促进转移性肝癌细胞的迁移。版权所有（C）2008 S. Karger AG，巴塞尔。
Background/Aim: p27(Kip1) (p27) is a member of the Cip/Kip family of cyclin/cyclin-dependent kinase inhibitors (CKIs), and its CKI-independent function regarding cell motility modulation has been discovered. However, it is controversial whether p27 promotes or inhibits cell migration. This study investigates the migration regulatory role of p27 in metastatic hepatocellular carcinoma (HCC) cells. Methods: RNA interference, RhoA-GTP pull-down assay, Western blots, immunostaining, transwell and wound-healing assays were used. Results: High levels of p27 and phosphorylated p27 (Ser10) were detected in metastatic HCC cells, MHCC97L and MHCC97H, when compared with nonmetastatic HCC cells, PLC and Hep3B. We hypothesized that p27 is responsible for metastasis-related migration in HCC cells and tested the hypothesis by using the p27 RNA interference approach. Increased RhoA activity was observed when p27 was knocked down in MHCC97L cells, which further led to stress fiber formation and decreased cell migration and wound healing. Moreover, high p27 and low stathmin expression of metastatic HCC cells indicated that migration inhibition by p27-stathmin interaction might not be the major regulatory pathway in metastatic HCC cells. Conclusion: p27 promotes cell migration in metastatic HCC cells through the regulation of RhoA activity. Copyright (C) 2008 S. Karger AG, Basel.