p27Kip1 Promotes Migration of Metastatic Hepatocellular Carcinoma Cells

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.