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

Authors
  • Lei, Jianjun
  • Fan, Lin
  • Wei, Guangbing
  • Chen, Xin
  • Duan, Wanxing
  • Xu, Qinhong
  • Sheng, Wei
  • Wang, Kang
  • Li, Xuqi
Type
Published Article
Journal
Tumor Biology
Publisher
SAGE Publications
Publication Date
Apr 01, 2015
Volume
36
Issue
4
Pages
3119–3126
Identifiers
DOI: 10.1007/s13277-014-2948-z
PMID: 25501705
Source
Medline
License
Unknown

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.

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