title: Sonic Hedgehog-GLI Family Zinc Finger 1 Signaling Pathway Promotes the Growth and Migration of Pancreatic Cancer Cells by Regulating the Transcription of Eukaryotic Translation Initiation Factor 5A2.
abstract: OBJECTIVE
  The Hh (hedgehog) signaling pathway is still waiting for further studies because its downstream molecular mechanism remains elusive. Because EIF5A2 (eukaryotic translation initiation factor 5A2) gene was up-regulated upon Gli1 (GLI family zinc finger 1) in pancreatic cancer (PC) cells, we speculated that this pathway might promote tumor progression through regulating EIF5A2.
  
  
  METHODS
  We investigated regulation effect of Hh signaling pathway to EIF5A2 gene transcription by Gli1 knockdown or overexpression in PC cell lines first. Then, the regulation mechanism of Gli1 to EIF5A2 gene was studied at transcription level. Finally, we studied cancer-promoting effects of Gli1-dependent EIF5A2 in PC cells.
  
  
  RESULTS
  The data showed that Gli1 up-regulated expression of EIF5A2 by promoting transcription via cis-acting elements in PC cells. Moreover, vimentin gene was up-regulated significantly by sonic hedgehog (SHh)/Gli1 expression increasing, and E-cadherin was significantly reduced. The EIF5A2 knockdown partially reversed cell proliferation and migration induced by artificial SHh overexpression and inhibited epithelial mesenchymal transition process in PC cells with SHh overexpression (P < 0.05).
  
  
  CONCLUSIONS
  Our data establish a novel transcription mechanism of Gli1 to EIF5A2 gene in cis-regulatory manner in PC cells. Thus, EIF5A2 oncogene effect could be incorporated into cancer-promoting molecular network upon Hh signaling pathway.
authors.affiliation: From the *Department of Gastroenterology, The Tenth People's Hospital of Shanghai, Tongji University, Shanghai; Departments of †Pathology and ‡Gastroenterology, The Second Hospital of Zhejiang University, Hangzhou, Zhejiang Province; and §Department of Hepato-Biliary and Pancreatic Oncology, Fudan University Shanghai Cancer Center, Minhang Branch, Shanghai, China.
authors.forename: Xuanfu
authors.initials: X
authors.lastname: Xu
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Weiqi
authors.initials: W
authors.lastname: Dai
authors.forename: Chuanyong
authors.initials: C
authors.lastname: Guo
authors.forename: Chuangao
authors.initials: C
authors.lastname: Xie
authors.forename: Shumei
authors.initials: S
authors.lastname: Wei
authors.forename: Shengli
authors.initials: S
authors.lastname: He
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Xu
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010448:Peptide Initiation Factors / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1; D016335:Zinc Fingers / Q000235:genetics; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D053823:Hedgehog Proteins; D015513:Oncogene Proteins; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D000071676:Zinc Finger Protein GLI1; D000097574:Eukaryotic Translation Initiation Factor 5A