title: p27Kip1 promotes migration of metastatic hepatocellular carcinoma cells.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  p27 promotes cell migration in metastatic HCC cells through the regulation of RhoA activity.
authors.affiliation: Department of Surgery, University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Xiao Qi
authors.initials: XQ
authors.lastname: Wang
authors.forename: Eric Lik Hang
authors.initials: EL
authors.lastname: Lui
authors.forename: Qi
authors.initials: Q
authors.lastname: Cai
authors.forename: Wilson Yik Pang
authors.initials: WY
authors.lastname: Ching
authors.forename: Karen Suk Yin
authors.initials: KS
authors.lastname: Liu
authors.forename: Ronnie Tung Ping
authors.initials: RT
authors.lastname: Poon
authors.forename: Sheung Tat
authors.initials: ST
authors.lastname: Fan
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D050760:Cyclin-Dependent Kinase Inhibitor p27; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000502:physiology*; D008113:Liver Neoplasms / Q000473:pathology*; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D020742:rhoA GTP-Binding Protein / Q000502:physiology*
chemical_list: C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; C066737:RHOA protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27; D020742:rhoA GTP-Binding Protein