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

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Tumor Biology

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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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, First Affiliated Hospital Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, China

    Jianjun Lei, Xin Chen, Wanxing Duan & Qinhong Xu

  2. Department of General Surgery, First Affiliated Hospital Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, China

    Lin Fan, Guangbing Wei, Wei Sheng, Kang Wang & Xuqi Li

Authors
  1. Jianjun Lei
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  2. Lin Fan
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  3. Guangbing Wei
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  4. Xin Chen
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  5. Wanxing Duan
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  6. Qinhong Xu
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  7. Wei Sheng
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  8. Kang Wang
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  9. Xuqi Li
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Correspondence to Xuqi Li.

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Jianjun Lei and Lin Fan made equal contributions to the study and should be considered co-first authors.

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Lei, J., Fan, L., Wei, G. et al. Gli-1 is crucial for hypoxia-induced epithelial-mesenchymal transition and invasion of breast cancer. Tumor Biol. 36, 3119–3126 (2015). https://doi.org/10.1007/s13277-014-2948-z

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  • DOI: https://doi.org/10.1007/s13277-014-2948-z

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