title: HIF-1α contributes to hypoxia-induced invasion and metastasis of esophageal carcinoma via inhibiting E-cadherin and promoting MMP-2 expression.
abstract: Hypoxia-inducible factor-1α (HIF-1α) has been found to enhance tumor invasion and metastasis, but no study has reported its action in esophageal carcinoma. The goal of this study was to explore the probable mechanism of HIF-1α in the invasion and metastasis of esophageal carcinoma Eca109 cells in vitro and in vivo. mRNA and protein expression of HIF-1α, E-cadherin and matrix metalloproteinase-2 (MMP-2) under hypoxia were detected by RT-PCR and Western blotting. The effects of silencing HIF-1α on E-cadherin, MMP-2 mRNA and protein expression under hypoxia or normoxia were detected by RT-PCR and Western blotting, respectively. The invasive ability of Eca109 cells was tested using a transwell chambers. We established an Eca109-implanted tumor model and observed tumor growth and lymph node metastasis. The expression of HIF-1α, E-cadherin and MMP-2 in xenograft tumors was detected by Western blotting. After exposure to hypoxia, HIF-1α protein was up-regulated, both mRNA and protein levels of E-cadherin were down-regulated and MMP-2 was up-regulated, while HIF-1α mRNA showed no significant change. SiRNA could block HIF-1α effectively, increase E-cadherin expression and inhibit MMP-2 expression. The number of invading cells decreased after HIF-1α was silenced. Meanwhile, the tumor volume was much smaller, and the metastatic rate of lymph nodes and the positive rate were lower in vivo. Our observations suggest that HIF-1α inhibition might be an effective strategy to weaken invasion and metastasis in the esophageal carcinoma Eca109 cell line.
authors.affiliation: Department of Radiotherapy, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
authors.forename: Shao-Wu
authors.initials: SW
authors.lastname: Jing
authors.forename: Ya-Di
authors.initials: YD
authors.lastname: Wang
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kuroda
authors.forename: Jing-Wei
authors.initials: JW
authors.lastname: Su
authors.forename: Guo-Gui
authors.initials: GG
authors.lastname: Sun
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.forename: Yun-Jie
authors.initials: YJ
authors.lastname: Cheng
authors.forename: Cong-Rong
authors.initials: CR
authors.lastname: Yang
mesh_terms: D000818:Animals; D015820:Cadherins / Q000037:antagonists & inhibitors* / Q000235:genetics; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000502:physiology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000502:physiology
chemical_list: D015820:Cadherins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D020778:Matrix Metalloproteinase 2