title: Hypoxia-induced snail expression through transcriptional regulation by HIF-1α in pancreatic cancer cells.
abstract: BACKGROUND
  Intratumoral hypoxia and epithelial-mesenchymal transition are involved in tumor invasion and metastasis.
  
  
  OBJECTIVE
  This study investigated the molecular mechanisms that relay the hypoxia signal into the epithelial-mesenchymal transition and metastasis.
  
  
  METHODS
  Morphology analysis and tumor cell migration and invasion assays were performed to detect phenotypic changes of pancreatic cancer cells under normoxic and hypoxic conditions after lentiviral HIF-1α shRNA transfection. Quantitative reverse transcription polymerase chain reaction, western blot, and immunohistochemistry were used to detect gene expression in pancreatic cancer cell lines and tissues or normal pancreatic tissues. Luciferase, gel shift, and ChIP assays were used to assess gene regulation.
  
  
  RESULTS
  Under hypoxic conditions, these tumor cells underwent typical morphological and molecular changes to epithelial-mesenchymal transition. Moreover, Snail expression was induced by hypoxic conditions and was regulated by HIF-1α expression at the transcriptional level through HIF-1α-binding to the second site of hypoxia-responsive elements of the Snail gene promoter. In addition, Snail expression was associated with HIF-1α expression in pancreatic cancer tissues, and expression of both was associated with tumor metastasis and poor patient survival.
  
  
  CONCLUSIONS
  Our study provides key evidence that HIF-1α and Snail are responsible for hypoxia-induced metastasis phenotypes in pancreatic cancer and that HIF-1α and Snail expression can be used as biomarkers to predict tumor metastasis and patient survival.
authors: Department of General Surgery, Fengxian Central Hospital, Shanghai, 201400, China, zhuzhu19820515@126.com.
authors: Guang-hui
authors: GH
authors: Zhu
authors: Chen
authors: C
authors: Huang
authors: Zheng-zhong
authors: ZZ
authors: Feng
authors: Xiu-hong
authors: XH
authors: Lv
authors: Zheng-jun
authors: ZJ
authors: Qiu
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000502:physiology*; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors
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