title: KAI1 inhibits HGF-induced invasion of pancreatic cancer by sphingosine kinase activity.
abstract: BACKGROUND
  KAI1/CD82 has been reported to attenuate the process of metastases in a variety of tumors; however, its mechanism of action in invasion has not been fully elucidated. The present study aimed to investigate the importance of KAI1 in invasion and its correlation with activation of sphingosine kinase (SPK) in human pancreatic cancer PANC1 and Miapaca-2 cell lines.
  
  
  METHODS
  The expression of KAI1 in PANC1 and Miapaca-2 cells, which was mediated by recombinant adenovirus (Ad-KAI1), was assessed by a flow cytometer and Western blotting. After successful infection was established, in vitro growth curve and invasive ability in Boyden Chamber assay were studied. The presence of KAI1 correlating with c-Met and SPK was detected by co-immunoprecipitation and [gamma-32P] ATP incorporation.
  
  
  RESULTS
  KAI1 genes had no significant effects on the curve representing cell growth. After infection with the KAI1 gene, decreased invasive ability in the Boyden Chamber assay was observed in PANC1 and Miapaca-2 cells that were induced by hepatocyte growth factor. Over-expression of KAI1 in the cells led to the deactivation of SPK and a decreased level of intracellular sphingosine-1-phosphate. No correlation was observed between c-Met and KAI1 during co-immunoprecipitation.
  
  
  CONCLUSIONS
  The results of this study for the first time demonstrated a regulatory role for KAI1 in SPK activation, which leads to decreased invasive ability in disease progression of human pancreatic cancer.
authors: State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital of Digestive Disease, Fourth Military Medical University, Xi'an 710032, China.
authors: Xu
authors: X
authors: Liu
authors: Xiao-Zhong
authors: XZ
authors: Guo
authors: Wei-Wei
authors: WW
authors: Zhang
authors: Zhuo-Zhuang
authors: ZZ
authors: Lu
authors: Qun-Wei
authors: QW
authors: Zhang
authors: Hai-Feng
authors: HF
authors: Duan
authors: Li-Sheng
authors: LS
authors: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D051861:Kangai-1 Protein / Q000235:genetics / Q000502:physiology*; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000473:pathology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000502:physiology; D014162:Transfection; D000099157:Sphingosine Kinase
chemical_list: D017228:Hepatocyte Growth Factor; D051861:Kangai-1 Protein; D017853:Phosphotransferases (Alcohol Group Acceptor); D019859:Proto-Oncogene Proteins c-met; D000099157:Sphingosine Kinase; C497688:CD82 protein, human