title: HIF-1α plays a role in the chemotactic migration of hepatocarcinoma cells through the modulation of CXCL6 expression.
abstract: OBJECTIVE
  Hypoxia promotes the progression and metastasis of hepatocellular carcinoma (HCC). Hypoxia inducible factor-α (HIF-1α) regulates the expression of various chemokines involved in tumor growth, angiogenesis and metastasis.
  
  
  METHODS
  The role of HIF-1α in HCC tumor growth and invasion and the prognosis of patients with HCC was investigated in cell lines and patient samples. HIF-1α mRNA and protein levels were assessed by qRT-PCR and western blotting. Silencing of HIF-1α downregulated the expression of granulocyte chemotactic protein-2 (GCP-2)/CXCL6, a CXC ELR+ chemokine, in HCC cells, and a luciferase assay showed that HIF-1α binds to a hypoxia response element in the promoter of CXCL6 and regulates its transcription. Induction of HIF-1α by hypoxia promoted the migration and invasion of HCC cells in vitro, and this effect was suppressed by an anti-CXCL6 antibody.
  
  
  RESULTS
  HIF-1α is upregulated in HCC cell lines and tissues and its effect on promoting invasion and metastasis is mediated by its direct interaction with the pro-angiogenic chemokine CXCL6. CXCL6 expression was associated with poor prognosis of HCC patients.
  
  
  CONCLUSIONS
  HIF-1α promotes HCC progression and metastasis by upregulating CXCL6 transcription in HCC cells, providing a potential novel therapeutic target for the treatment of HCC.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tian
authors.forename: Peixin
authors.initials: P
authors.lastname: Huang
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Zhao
authors.forename: Wenqing
authors.initials: W
authors.lastname: Tang
authors.forename: Jinglin
authors.initials: J
authors.lastname: Xia
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D054427:Chemokine CXCL6 / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D000860:Hypoxia / Q000235:genetics; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: C515503:CXCL6 protein, human; D054427:Chemokine CXCL6; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit