title: STAT3 activation mediates epithelial-to-mesenchymal transition in human hepatocellular carcinoma cells.
abstract: OBJECTIVE
  Epithelial-to-mesenchymal transition (EMT) is critical for the development of the invasion and metastasis in human cancers. Recently, signal transducer and activator of transcription 3 (STAT3) activation has been linked to EMT program in breast cancer. However, the actual association of STAT3 activation with EMT, and its mediated tumor invasion and metastasis remains elusive in hepatocellular carcinoma (HCC). The aim of this study was to investigate the correlation between STAT3 activation and EMT, as well as the underlying mechanism involved in HCC progression.
  
  
  METHODS
  We treated SMMC-7721 cells with a known STAT3 activator, epithelial growth factor (EGF); in the absence or presence of JSI-124, a selective STAT3 inhibitor. The EMT-associated morphologic and molecular changes of cells were analyzed. The EMT-mediated HCC cell invasion, migration and adhesion were evaluated.
  
  
  RESULTS
  In this study, we found that STAT3 activation induced by EGF was associated significantly with morphologic changes, cytoskeleton rearrangement and molecular changes consistent with EMT in SMMC-7721 cells; STAT3 activation-mediated EMT may be transcriptionally induced by Twist. STAT3 activation-mediated EMT also promoted HCC cell invasion, migration and adhesion significantly.
  
  
  CONCLUSIONS
  In summary, our study show for the first time that STAT3 activation may induce invasion and metastasis through the mediation of EMT in HCC cells. Activated STAT3 and EMT markers can serve as molecular targets for HCC treatment.
authors.forename: Chuan-hai
authors.initials: CH
authors.lastname: Zhang
authors.forename: Feng-Lin
authors.initials: FL
authors.lastname: Guo
authors.forename: Ge-Liang
authors.initials: GL
authors.lastname: Xu
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Jia
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Ge
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D048430:Cell Shape; D004815:Epidermal Growth Factor / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014315:Triterpenes / Q000494:pharmacology
chemical_list: D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014315:Triterpenes; D004815:Epidermal Growth Factor; C038106:cucurbitacin I