Li Li, Zhao Fenglong, Lu Juan, Li Tingting, Yang Hong, Wu Chunhui, Liu Yiyao
Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, P.R. China.
PLoS One. 2014 Apr 23;9(4):e95912. doi: 10.1371/journal.pone.0095912. eCollection 2014.
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.
Notch-1信号通路的异常激活已被证明与癌症的发生和发展相关。然而，Notch-1信号通路在乳腺癌恶性行为中的具体作用及潜在机制仍知之甚少。在本研究中，我们采用多种细胞和分子方法，证明Notch-1信号通路的激活促进了MDA-MB-231细胞的恶性行为，如细胞增殖增加、集落形成、黏附、迁移和侵袭，并抑制细胞凋亡；而该信号通路的失活则导致上述恶性细胞行为的逆转。此外，我们发现Notch-1信号通路的激活触发了NF-κB信号通路的激活，并上调了NF-κB靶基因的表达，包括MMP-2/-9、VEGF、Survivin、Bcl-xL和Cyclin D1。这些结果表明，Notch-1信号通路在促进乳腺癌恶性表型中起重要作用，这可能部分通过激活NF-κB信号通路介导。我们的结果进一步表明，靶向Notch-1信号通路可能成为阻止乳腺癌进展的一种新方法。
