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

• Published in: PloS one Vol. 9; no. 4; p. e95912
• Main Authors: Li, Li, Zhao, Fenglong, Lu, Juan, Li, Tingting, Yang, Hong, Wu, Chunhui, Liu, Yiyao
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.04.2014; Public Library of Science (PLoS)
• 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; United States > US; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0095912

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.