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TNF‐α inhibits breast cancer cells adhesion via HIF‐1α mediated VASP suppression
Author(s) -
Su Ke,
Tian Yihao,
Wang Jing,
Shi Wentao,
Zhang Jingwei,
Wei Lei
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.905.4
Subject(s) - gene knockdown , tumor necrosis factor alpha , downregulation and upregulation , metastasis , cancer research , adhesion , mtt assay , cell adhesion , chemistry , phosphoprotein , microbiology and biotechnology , biology , cancer , medicine , immunology , apoptosis , phosphorylation , gene , biochemistry , organic chemistry
TNF‐α is implicated in tumor invasion and metastasis, but its mechanism remains elusive. Herein we provide a study underlying the role of TNF‐α in inhibiting MCF‐7 breast cancer cells adhesion which initiate breast cancer metastasis process. In this research, to evaluate the effect of TNF‐α (100 ng/ml) on MCF‐7 cells adhesion ability, MTT assay were performed. We observed that TNF‐α administration led to decreased adhesion ability of MCF‐7 cells in a dose dependent manner. Secondly, TNF‐α attenuates MCF‐7 cells adhesion may via suppressing VASP (vasodilator‐stimulated phosphoprotein) protein expression levels analysing by westernblot. Additionally, TNF‐α had no obvious effect on HIF‐1α mRNA expression levels analysing by Real‐time PCR. In contrast, TNF‐α upregulated HIF‐1α protein expression levels. Furthermore, using promoter assay, EMSA and ChIP approaches we identified that VASP as a direct target gene of HIF‐1α and HIF‐1α repress VASP at transcription level. Consistently, knockdown of HIF‐1α abrogated TNF‐α mediated VASP suppression. Collectively, we provided evidence that HIF‐1α may acts downstream of TNF‐α to inhibit VASP expression and modulate the adhesion of breast cancer cells. (This work was supported by National Natural Sciences Foundation of China under Grant No.30971132, 81172043 and the Hubei Science Foundation under Grant No. 2009CDA074)