title: Suppression of growth and migration by blocking the Hedgehog signaling pathway in gastric cancer cells.
abstract: OBJECTIVE
  Previous studies have indicated that Hedgehog signaling is essential for gastric cancer development, but its precise role is still unclear. The aim of this study was to clarify the role of Hedgehog signaling in gastric cancer development.
  
  
  METHODS
  The expression of key Hedgehog signaling components in clinical samples of sequential gastric cancer stages was assessed by immunohistochemistry. The roles and regulatory mechanisms of Hedgehog signaling in human gastric cancer cells and normal gastric epithelial cells were investigated using multiple cell biological approaches and cDNA microarray analyses.
  
  
  RESULTS
  Hedgehog signaling was found to be abnormally activated in a ligand-independent manner during gastric cancer development. Gli1 over-expression and reduced SuFu expression were found to be typical events in gastric cancer tissues. Gli1 over-expression was found to correlate with a poorly differentiated histology, advanced clinical stage, membrane serosa infiltration and lymph node metastasis in patients with gastric cancer. Data obtained from multiple cell biological assays showed that human gastric cancer cells require active Hedgehog signaling for survival, proliferation, migration and colony formation. N-Shh treatment significantly enhanced the migration, invasion and colony formation of gastric cancer cells. Moreover, the results of cDNA microarray analyses indicated that after treatment with cyclopamine or GANT61 (inhibitors of Hedgehog signaling), differentially expressed genes in gastric cancer cells were enriched in the apoptosis and MAPK pathways. Inhibitors of the Hedgehog pathway were found to suppress gastric cancer cell growth via apoptosis induction.
  
  
  CONCLUSIONS
  Our findings indicate a vital role of the activated Hedgehog signaling pathway in promoting gastric initiation and progression. The Hedgehog signaling pathway may serve as a target for gastric cancer therapy.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, No.17 Yongwai street, Donghu district, Nanchang, 330006, China.
authors.forename: Runwei
authors.initials: R
authors.lastname: Yan
authors.forename: Xiang
authors.initials: X
authors.lastname: Peng
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Yuan
authors.forename: Dengliang
authors.initials: D
authors.lastname: Huang
authors.forename: Jiang
authors.initials: J
authors.lastname: Chen
authors.forename: Quqin
authors.initials: Q
authors.lastname: Lu
authors.forename: Nonghua
authors.initials: N
authors.lastname: Lv
authors.forename: Shiwen
authors.initials: S
authors.lastname: Luo
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D015513:Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014704:Veratrum Alkaloids / Q000494:pharmacology; D000071676:Zinc Finger Protein GLI1
chemical_list: D053823:Hedgehog Proteins; D015513:Oncogene Proteins; C509239:SHH protein, human; D015534:Trans-Activators; D014704:Veratrum Alkaloids; D000071676:Zinc Finger Protein GLI1; C000541:cyclopamine
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