title: Gli1 promotes transforming growth factor-beta1- and epidermal growth factor-induced epithelial to mesenchymal transition in pancreatic cancer cells.
abstract: BACKGROUND
  The Hedgehog signaling pathway and its key target effector Gli1 are linked closely to the development of the epithelial to mesenchymal transition (EMT) in many cancers. The definite function of Gli1 in regulating the EMT of pancreatic cancer (PC), however, is still unclear.
  
  
  METHODS
  At the cell and tissue levels, we investigated the role of Gli1 in the initiation of EMT in PC with and without external stimulus treatments.
  
  
  RESULTS
  The immunohistochemistry results showed that Gli1 was associated positively with MMP9 but not with E-cad or Vimentin. Gli1 expression was associated positively with tumor T (P = .025) and Union for International Cancer Control stage (P = .032), whereas MMP9 expression was associated positively with lymph node metastasis (P = .017) and Union for International Cancer Control stage (P = .006). Furthermore, patients with Gli1 and MMP9 coexpression had poor overall survival (P = .015). Silencing of Gli1 alone without external stimulus had no effect on EMT but inhibited transforming growth factor-beta1 (TGFβ1)- and epidermal growth factor (EGF)-induced EMT in PANC-1, AsPC-1, and BxPC-3 PC cell lines, along with the inhibition of TGFβ1- and EGF-induced EMT-like cell morphology and invasion, down-regulation of E-cad, and up-regulation of MMP9 and Vimentin in those 3 cell lines, respectively.
  
  
  CONCLUSIONS
  Gli1 silencing alone has no effect on EMT initiation; however, it exerts a protumor role in the aggressive invasion of PC cells by promoting TGFβ1- and EGF-induced EMT.
authors.affiliation: Department of General Surgery, Gastrointestinal Surgery, the First Hospital, China Medical University, Shenyang, China; Department of General Surgery, the People's Hospital of Liaoning Province, Shenyang, China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Gastrointestinal Surgery, the First Hospital, China Medical University, Shenyang, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Sheng
authors.affiliation: Department of General Surgery, Gastrointestinal Surgery, the First Hospital, China Medical University, Shenyang, China. Electronic address: cmumingdong@sohu.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Dong
authors.affiliation: Department of Surgical Oncology, the First Hospital, China Medical University, Shenyang, China.
authors.forename: Xiaoshen
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of General Surgery, the People's Hospital of Liaoning Province, Shenyang, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Department of Cell Biology, China Medical University, Shenyang, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D015820:Cadherins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000096:biosynthesis; D000071676:Zinc Finger Protein GLI1
chemical_list: D015820:Cadherins; C400551:GLI1 protein, human; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D014746:Vimentin; D000071676:Zinc Finger Protein GLI1; D004815:Epidermal Growth Factor; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9