Notch-1 signaling promotes the malignant features of human breast cancer through NF-κB activation

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 stu...

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Bibliographic Details
Published in:PloS one 2014-04, Vol.9 (4), p.e95912-e95912
Main Authors: Li, Li, Zhao, Fenglong, Lu, Juan, Li, Tingting, Yang, Hong, Wu, Chunhui, Liu, Yiyao
Format: Article
Language:English
Subjects:
Aberration
Activation
Angiogenesis
Apoptosis
Bcl-x protein
Biology and Life Sciences
Biophysics
Breast cancer
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cancer
Cancer therapies
Cell Adhesion
Cell adhesion & migration
Cell culture
Cell growth
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cyclin D1
Deactivation
Female
Gelatinase A
Gene expression
Gene Expression Regulation, Neoplastic
Genotype & phenotype
Humans
Life sciences
Ligands
Medicine and Health Sciences
Metastasis
NF-kappa B - metabolism
NF-κB protein
Notch1 protein
Pancreatic cancer
Penicillin
Polyclonal antibodies
Prostate cancer
Proteins
Receptor, Notch1 - genetics
Receptor, Notch1 - metabolism
Signal Transduction
Signaling
Survivin
Tumors
Vascular endothelial growth factor
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Summary: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-κB signaling pathway and up-regulated the expression of NF-κB 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-κB signaling pathway. Our results further suggest that targeting Notch-1 signaling pathway may become a newer approach to halt the progression of breast cancer.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0095912