Notch-4 silencing inhibits prostate cancer growth and EMT via the NF-κB pathway

Abstract

Epithelial-mesenchymal transition (EMT) is implicated in the metastasis of human prostate cancer (PCa). Notch signaling has been established as a regulator of EMT. Notch-4 has emerged as a mammary proto-oncogene and a target in several cancers. However, the role and the mechanism of action of Notch-4 in PCa are still unclear. In the present study, we first observed a marked increase in Notch-4 expression in the PCa cell lines DU145, PC3 and LnCAP compared with the non-malignant prostate epithelial cell line RWPE1. Knocking down the expression of Notch-4 suppressed the viability and proliferation in the PCa cell lines DU145 and PC3. Also, further study showed that a decline in Notch-4 significantly promoted apoptosis in PC3 cells. Notch-4 silencing also resulted in decreased cell migration and invasion and affected the expression of EMT markers. We hypothesized that Notch-4 ablation suppresses the activity of NF-κB, so we used PMA to stimulate NF-κB p50 and p65 activation in PC3 cells. The results indicate that PMA treatment impaired the action of Notch-4 ablation in the biology of PC3 cells including cell growth, apoptosis, migration, invasion and EMT. The results of the present study show that RNAi targeting against Notch-4 expression suppresses PCa progression.

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Correspondence to Jianwei Zhang.

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Zhang, J., Kuang, Y., Wang, Y. et al. Notch-4 silencing inhibits prostate cancer growth and EMT via the NF-κB pathway. Apoptosis 22, 877–884 (2017). https://doi.org/10.1007/s10495-017-1368-0

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Keywords

  • Prostate cancer
  • Epithelial-mesenchymal transition
  • Notch-4
  • NF-kB