title: AKT/GSK-3β regulates stability and transcription of snail which is crucial for bFGF-induced epithelial-mesenchymal transition of prostate cancer cells.
abstract: BACKGROUND
  Epithelial-mesenchymal transition (EMT) plays a pivotal role in the development of metastatic cancers. Basic fibroblast growth factor (bFGF) is significantly elevated in metastatic prostate cancers, which has been mentioned mainly to induce EMT in normal cells. However, there is no description about bFGF induced EMT and its underlying mechanism in prostate cancer cells.
  
  
  METHODS
  Western blotting, immunofluorescence and qRT-PCR assays were used to study protein or mRNA expression profiles of the EMT. Wound healing scratch, migration and invasion assays were used to test the motility of cells undergoing EMT. More methods were used to explore the underlying mechanisms.
  
  
  RESULTS
  We demonstrated that bFGF promoted EMT and motility of human prostate cancer PC-3 cells. Both protein and mRNA expression of Snail were rapidly increased after bFGF treatment. Ectopic expression of Snail triggered EMT and enhanced cell motility in PC-3 cells, and knockdown of Snail almost abolished bFGF induced EMT, suggesting the critical role of Snail. Mechanistic study demonstrated that bFGF promoted the stability, nuclear localization and transcription of Snail by inhibiting the activity of glycogen synthase kinase 3 beta (GSK-3β) through phosphatidylinositide 3 kinases (PI3K)/protein kinase B (AKT) signaling pathway.
  
  
  CONCLUSIONS
  It is concluded that bFGF can promote EMT and motility of PC-3 cells, and AKT/GSK-3β signaling pathway controls the stability, localization and transcription of Snail which is crucial for this bFGF induced EMT.
  
  
  CONCLUSIONS
  To our knowledge, this is the first study to demonstrate that bFGF can induce EMT via AKT/GSK-3β/Snail signaling pathway in prostate cancer cells.
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong, China.
authors.forename: Zong-Cai
authors.initials: ZC
authors.lastname: Liu
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong, China.
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Wang
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Cancer Research Institute, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou 510095, Guangdong, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Chen
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong, China.
authors.forename: Dan-Yang
authors.initials: DY
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong, China. Electronic address: tcsh@jnu.edu.cn.
authors.forename: Shao-Hui
authors.initials: SH
authors.lastname: Cai
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong, China. Electronic address: dujun@mail.sysu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Du
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
keywords: Basic fibroblast growth factor; Epithelial–mesenchymal transition; Invasion; Prostate cancer; Snail