title: 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.
authors.affiliation: Department of Urology Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. jianweizhanghn@163.com.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Youlin
authors.initials: Y
authors.lastname: Kuang
authors.affiliation: Department of Urology Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Urology Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
authors.forename: Quanquan
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Ren
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D020868:Gene Silencing; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D000090063:Proto-Oncogene Mas; D000074562:Receptor, Notch4 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C000715470:MAS1 protein, human; D016328:NF-kappa B; C106075:NOTCH4 protein, human; D000090063:Proto-Oncogene Mas; D000074562:Receptor, Notch4
keywords: Epithelial-mesenchymal transition; NF-kB; Notch-4; Prostate cancer