title: CXCR4 promotes GSK3β expression in pancreatic cancer cells via the Akt pathway.
abstract: BACKGROUND
  CXCR4 and glycogen synthase kinase-3β (GSK3β) promote proliferation and invasion of pancreatic cancer. Inhibition of CXCR4 suppresses GSK3β expression. However, the molecular mechanism by which CXCR4 contributes to human pancreatic cancer metastasis is not completely understood. In this study, therefore, we analyzed the effect of CXCR4 on GSK3β expression and its molecular mechanism.
  
  
  METHODS
  PANC-1 and SW-1990 cells were used in this study. PANC-1 and SW-1990 cell lines which stably expressed upregulated or downregulated CXCR4 were used for further study. Western blotting was employed to detected the expression of CXCR4, GSK3β and MMP-2. Cell invasion assay was used to detect the effect of the Akt pathway on CXCR4-induced GSK3β expression.
  
  
  RESULTS
  Overexpression of CXCR4 promoted GSK3β expression and silencing of CXCR4 suppressed GSK3β expression. Overexpression of CXCR4 activated cyclin D1 and p-Akt expression, but inhibited p21 expression. Silencing of CXCR4 had the reverse effect. CXCR4 promoted GSK3β expression and PANC-1 invasion by Akt signaling. CXCR4 upregulated GSK3β expression, at least in part, at the level of transcription.
  
  
  CONCLUSIONS
  CXCR4 promotes GSK3β expression via the Akt cell signaling pathway in pancreatic cancer cells.
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, 223300, Jiangsu, People's Republic of China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Ma
authors.forename: Qianjun
authors.initials: Q
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Pan
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000096:biosynthesis*; D015398:Signal Transduction
chemical_list: C530104:CCND1 protein, human; C493956:CDKN1A protein, human; C527276:CXCR4 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019718:Receptors, CXCR4; D019938:Cyclin D1; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3