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- Title
HIF-1α Acts Downstream of TNF-α to Inhibit Vasodilator-Stimulated Phosphoprotein Expression and Modulates the Adhesion and Proliferation of Breast Cancer Cells.
- Authors
Su, Ke; Tian, Yihao; Wang, Jing; Shi, Wentao; Luo, Daji; Liu, Jian; Tong, Zan; Wu, Junzhu; Zhang, Jingwei; Wei, Lei
- Abstract
Metastasis is the leading cause of death in breast cancer patients. Recent evidence suggests that inflammation-related cytokine tumor necrosis factor-alpha (TNF-α) is implicated in tumor invasion and metastasis, but the mechanism of its involvement remains elusive. In this study, we employed MCF-7 breast cancer cells as an experimental model to demonstrate that TNF-α inhibits breast cancer cell adhesion and cell proliferation through hypoxia inducible factor-1alpha ( HIF-1α) mediated suppression of vasodilator-stimulated phosphoprotein ( VASP). We observed that TNF-α treatment attenuated the adhesion and proliferation of MCF-7 cells it also dramatically increased HIF-1α expression and decreased VASP expression. Through a variety of approaches, including promoter assay, electrophoretic mobility shift assay (EMSA), and chromatin immunoprecipitation (ChIP), we identified VASP as a direct target gene of HIF-1α. In addition, we confirmed that HIF-1α mediated the repression of VASP expression by TNF-α in MCF-7 cells. We also demonstrated that exogenous VASP expression or knockdown of HIF-1α relieved TNF-α induced inhibition of cell adhesion and proliferation. We identified a novel TNF-α/HIF-1α/VASP axis in which HIF-1α acts downstream of TNF-α to inhibit VASP expression and modulate the adhesion and proliferation of breast cancer cells. These data provide new insight into the potential anti-tumor effects of TNF-α.
- Subjects
BREAST cancer; TUMOR necrosis factors; CANCER invasiveness; CANCER cell proliferation; CELL adhesion; VASODILATOR-stimulated phosphoprotein; HYPOXIA-inducible factor 1
- Publication
DNA & Cell Biology, 2012, Vol 31, Issue 6, p1078
- ISSN
1044-5498
- Publication type
Article
- DOI
10.1089/dna.2011.1563