HIF-1α contributes to hypoxia-induced invasion and metastasis of esophageal carcinoma via inibiting E-cadherin and promoting MMP-2 expression

Shao Wu Jing, Ya Di Wang, Masahiro Kuroda, Jing Wei Su, Guo Gui Sun, Qing Liu, Yun Jie Cheng, Cong Rong Yang

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Hypoxia-inducible factor-1a (HIF-1a) 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-1a in the invasion and metastasis of esophageal carcinoma Eca109 cells in vitro and in vivo. mRNA and protein expression of HIF-1a, E-cadherin and matrix metalloproteinase-2 (MMP-2) under hypoxia were detected by RT-PCR and Western blotting. The effects of silencing HIF-1a 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-1a, E-cadherin and MMP-2 in xenograft tumors was detected by Western blotting. After exposure to hypoxia, HIF-1a protein was up-regulated, both mRNA and protein levels of E-cadherin were down-regulated and MMP-2 was up-regulated, while HIF-1a mRNA showed no significant change. SiRNA could block HIF-1a effectively, increase E-cadherin expression and inhibit MMP-2 expression. The number of invading cells decreased after HIF-1a 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-1a inhibition might be an effective strategy to weaken invasion and metastasis in the esophageal carcinoma Eca109 cell line.

Original languageEnglish
Pages (from-to)399-407
Number of pages9
JournalActa Medica Okayama
Volume66
Issue number5
Publication statusPublished - 2012

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Matrix Metalloproteinase 2
Cadherins
Tumors
Neoplasm Metastasis
Carcinoma
Messenger RNA
Proteins
Heterografts
Western Blotting
Cells
Hypoxia
Neoplasms
Lymph Nodes
Polymerase Chain Reaction
Tumor Burden
Cell Count

Keywords

  • Esophageal carcinoma
  • Hypoxia-inducible factor-1α
  • Invasion
  • Metastasis

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

HIF-1α contributes to hypoxia-induced invasion and metastasis of esophageal carcinoma via inibiting E-cadherin and promoting MMP-2 expression. / Jing, Shao Wu; Wang, Ya Di; Kuroda, Masahiro; Su, Jing Wei; Sun, Guo Gui; Liu, Qing; Cheng, Yun Jie; Yang, Cong Rong.

In: Acta Medica Okayama, Vol. 66, No. 5, 2012, p. 399-407.

Research output: Contribution to journalArticle

Jing, Shao Wu ; Wang, Ya Di ; Kuroda, Masahiro ; Su, Jing Wei ; Sun, Guo Gui ; Liu, Qing ; Cheng, Yun Jie ; Yang, Cong Rong. / HIF-1α contributes to hypoxia-induced invasion and metastasis of esophageal carcinoma via inibiting E-cadherin and promoting MMP-2 expression. In: Acta Medica Okayama. 2012 ; Vol. 66, No. 5. pp. 399-407.
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