Notch1 suppresses prostate cancer cell invasion via the metastasis‑associated 1‑KiSS‑1 metastasis‑suppressor pathway

Deng,Gang; Zheng,Xiaoliang; Jiang,Peiwu; Chen,Kean; Wang,Xiaoju; Jiang,Kang; Zhang,Wenjun; Tu,Linglan; Yan,Dongmei; Ma,Libin; Ma,Shenglin

doi:10.3892/ol.2017.6761

Notch1 suppresses prostate cancer cell invasion via the metastasis‑associated 1‑KiSS‑1 metastasis‑suppressor pathway

Authors:
- Gang Deng
- Xiaoliang Zheng
- Peiwu Jiang
- Kean Chen
- Xiaoju Wang
- Kang Jiang
- Wenjun Zhang
- Linglan Tu
- Dongmei Yan
- Libin Ma
- Shenglin Ma
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Affiliations: Department of Urology, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310006, P.R. China, Center for Molecular Medicine, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310000, P.R. China, Zhejiang Chinese Medical University and Hangzhou First People's Hospital, Hangzhou, Zhejiang 310006, P.R. China, Department of Nephrology, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310006, P.R. China, Department of Oncology, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310006, P.R. China
Published online on: August 17, 2017 https://doi.org/10.3892/ol.2017.6761
Pages: 4477-4482
Copyright: © Deng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Notch1 is a type‑1 transmembrane receptor which has been demonstrated to be involved in proliferation in various organisms. A number of studies have proposed that Notch signaling may be aberrantly activated, thus contributing to development, invasion and metastasis in a variety of human cancers. In the present study, the function and mechanism of Notch1 in human prostate cancer (PCa) LNCaP cells in vitro was investigated. Notch1 and cleaved‑Notch1 expression were evaluated in human PCa cell lines, including LNCaP, PC‑3 and DU 145, and the human prostate epithelial RWPE‑1 cell line. LNCaP cells were transfected with Notch1‑targeting short hairpin RNAs (shRNAs) and the level of proliferation, the ability to invade and the expression of genes associated with cancer cell invasion were subsequently investigated. Notch1 was highly expressed in LNCaP, PC‑3 and DU 145 cells compared with RWPE‑1 cells, while cleaved‑Notch1 was expressed in LNCaP, PC‑3 and DU 145 cells, and only to a minimal extent in RWPE‑1 cells. Knockdown of Notch1 by shRNA in LNCaP cells markedly decreased cell invasion through Matrigel and inhibited cell proliferation 48 h following transfection. Reverse transcription‑quantitative polymerase chain reaction analysis indicated that Notch1‑knockdown resulted in a significant reduction of metastasis‑associated 1 (MTA1) and increase of KiSS‑1 metastasis‑suppressor (KISS‑1), mitogen‑activated protein kinase 4 (MKK4) and cluster of differentiation 82 (KAI1). The present data demonstrated that expression of Notch1 was significantly associated with the invasion of prostate cancer. Knockdown of Notch1 decreased the invasive ability of LNCaP cells, which may be caused by downregulating MTA1 and upregulating KISS‑1, MKK4 and KAI1. These findings indicated that targeting Notch1 may provide a novel method of suppressing or treating metastasis in prostate cancer.

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