期刊
TUMOR BIOLOGY
卷 36, 期 4, 页码 3119-3126出版社
SAGE PUBLICATIONS LTD
DOI: 10.1007/s13277-014-2948-z
关键词
Breast carcinoma; Invasion; Tumor; Epithelial-mesenchymal transition; Hypoxia; Gli-1
类别
Hypoxia can induce HIF-1 alpha 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-1 alpha or Gli-1-specific small interfering RNA (siRNA) and cultured under a normoxic or hypoxic condition. The relative levels of HIF-1 alpha, 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-1 alpha translation and Gil-1 expression. Knockdown of HIF-1 alpha mitigated hypoxia-modulated Gil-1, vimentin and E-cadherin expression, and invasion ofMDA-MB-231 cells. Knockdown of Gil-1 did not significantly change hypoxia-upregulated HIF-1 alpha 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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