title: Gli-1 is crucial for hypoxia-induced epithelial-mesenchymal transition and invasion of breast cancer.
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.
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Lei
authors.forename: Lin
authors.initials: L
authors.lastname: Fan
authors.forename: Guangbing
authors.initials: G
authors.lastname: Wei
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Wanxing
authors.initials: W
authors.lastname: Duan
authors.forename: Qinhong
authors.initials: Q
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Sheng
authors.forename: Kang
authors.initials: K
authors.lastname: Wang
authors.forename: Xuqi
authors.initials: X
authors.lastname: Li
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D015820:Cadherins / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014746:Vimentin / Q000096:biosynthesis; D000071676:Zinc Finger Protein GLI1
chemical_list: D015820:Cadherins; C400551:GLI1 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D014746:Vimentin; D000071676:Zinc Finger Protein GLI1