Tumor Biology

, Volume 36, Issue 4, pp 3119–3126 | Cite as

Gli-1 is crucial for hypoxia-induced epithelial-mesenchymal transition and invasion of breast cancer

  • Jianjun Lei
  • Lin Fan
  • Guangbing Wei
  • Xin Chen
  • Wanxing Duan
  • Qinhong Xu
  • Wei Sheng
  • Kang Wang
  • Xuqi Li
Research Article

Abstract

Hypoxia can induce HIF-1α expression and promote the epithelial-mesenchymal transition (EMT) and invasion of cancer cells. However, their mechanisms remain unclear. The objective of this study was to evaluate the role of Gli-1, an effector of the Hedgehog pathway, in the hypoxia-induced EMT and invasion of breast cancer cells. Human breast cancer MDA-MB-231 cells were transfected with HIF-1α or Gli-1-specific small interfering RNA (siRNA) and cultured under a normoxic or hypoxic condition. The relative levels of HIF-1α, Gli-1, E-cadherin, and vimentin in the cells were characterized by quantitative RT-PCR and Western blot assays, and the invasion of MDA-MB-231 cells was determined. Data was analyzed by Student T test, one-way ANOVA, and post hoc LSD test or Mann-Whitney U when applicable. We observed that hypoxia significantly upregulated the relative levels of vimentin expression, but downregulated E-cadherin expression and promoted the invasion of MDA-MB-231 cells, associated with upregulated HIF-1α translation and Gil-1 expression. Knockdown of HIF-1α mitigated hypoxia-modulated Gil-1, vimentin and E-cadherin expression, and invasion of MDA-MB-231 cells. Knockdown of Gil-1 did not significantly change hypoxia-upregulated HIF-1α translation but completely eliminated hypoxia-modulated vimentin and E-cadherin expression and invasion of MDA-MB-231 cells. These data indicate that Gil-1 is crucial for hypoxia-induced EMT and invasion of breast cancer cells and may be a therapeutic target for intervention of breast cancer metastasis.

Keywords

Breast carcinoma Invasion Tumor Epithelial-mesenchymal transition Hypoxia Gli-1 

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Jianjun Lei
    • 1
  • Lin Fan
    • 2
  • Guangbing Wei
    • 2
  • Xin Chen
    • 1
  • Wanxing Duan
    • 1
  • Qinhong Xu
    • 1
  • Wei Sheng
    • 2
  • Kang Wang
    • 2
  • Xuqi Li
    • 2
  1. 1.Department of Hepatobiliary SurgeryFirst Affiliated Hospital Medical College of Xi’an Jiaotong UniversityXi’anChina
  2. 2.Department of General SurgeryFirst Affiliated Hospital Medical College of Xi’an Jiaotong UniversityXi’anChina

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