Notch-1 Signaling Promotes the Malignant Features of Human Breast Cancer through NF-kappa B Activation

作者：Li, Li; Zhao, Fenglong; Lu, Juan; Li, Tingting; Yang, Hong; Wu, Chunhui; Liu, Yiyao^*

来源：PLos One, 2014, 9(4): e95912.

DOI：10.1371/journal.pone.0095912

• HUMAN PROSTATE-CANCER
• DOWN-REGULATION
• CELL INVASION
• PROTEIN EXPRESSION
• GROWTH
• DIFFERENTIATION
• INHIBITION
• MIGRATION
• APOPTOSIS
• PROLIFERATION

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.

• 出版日期2014-4-23
• 单位电子科技大学