期刊
PLOS ONE
卷 9, 期 4, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0095912
关键词
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资金
- National Natural Science Foundation of China [11272083, 81071257, 81201192, 81101147]
- New Century Excellent Talents Program in Chinese Universities [NCET-09-0263]
- Sichuan Youth Science and Technology Foundation of China [2010JQ0004]
- Postdoctal Program of China [2011M501297, 2012T50715]
- Fundamental Research Funds for Central Universities [ZYGX2010X019, ZYGX2010J101, ZYGX2011J099]
The aberrant activation of Notch-1 signaling pathway has been proven to be associated with the development and progression of cancers. However, the specific roles and the underlying mechanisms of Notch-1 signaling pathway on the malignant behaviors of breast cancer are poorly understood. In this study, using multiple cellular and molecular approaches, we demonstrated that activation of Notch-1 signaling pathway promoted the malignant behaviors of MDA-MB-231 cells such as increased cell proliferation, colony formation, adhesion, migration, and invasion, and inhibited apoptosis; whereas deactivation of this signaling pathway led to the reversal of the aforementioned malignant cellular behaviors. Furthermore, we found that activation of Notch-1 signaling pathway triggered the activation of NF-kappa B signaling pathway and up-regulated the expression of NF-kappa B target genes including MMP-2/-9, VEGF, Survivin, Bcl-xL, and Cyclin D1. These results suggest that Notch-1 signaling pathway play important roles in promoting the malignant phenotype of breast cancer, which may be mediated partly through the activation of NF-kappa B signaling pathway. Our results further suggest that targeting Notch-1 signaling pathway may become a newer approach to halt the progression of breast cancer.
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