4-HPR impairs bladder cancer cell migration and invasion by interfering with the Wnt5a/JNK and Wnt5a/MMP-2 signaling pathways

Cao,Yuanfei; Wang,Xiaolong; Xu,Chang; Gao,Zhengyan; Zhou,Haihong; Wang,Yongzhi; Cao,Rui; Liu,Tao; Liu,Tongzu

doi:10.3892/ol.2016.4908

4-HPR impairs bladder cancer cell migration and invasion by interfering with the Wnt5a/JNK and Wnt5a/MMP-2 signaling pathways

Authors:
- Yuanfei Cao
- Xiaolong Wang
- Chang Xu
- Zhengyan Gao
- Haihong Zhou
- Yongzhi Wang
- Rui Cao
- Tao Liu
- Tongzu Liu
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Affiliations: Department of Urology, Taizhou People's Hospital of Jiangsu Province, Taizhou, Jiangsu 225300, P.R. China, Department of Urology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China
Published online on: July 22, 2016 https://doi.org/10.3892/ol.2016.4908
Pages: 1833-1839
Copyright: © Cao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In order to identify the anti-invasive and anti-metastatic effect of the synthetic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR) on the human bladder cancer EJ cell line, and to study its impact on the expression of wingless-type mouse mammary tumor virus integration site family, member 5a (Wnt5a), the phosphorylation of c‑Jun N‑terminal kinase (JNK), the expression levels of matrix metalloproteinase-2 (MMP-2), and the migration and invasion of EJ cells, migration and Matrigel invasion assays, as well as western blot analyses, were used in the present study. The results of the migration and Matrigel invasion assays indicated that the inhibitor of JNK SP600125 could inhibit the effect of 4‑HPR on EJ cells. The expression of Wnt5a and MMP‑2, and the phosphorylation of JNK, were analyzed by western blotting. The data revealed that 4-HPR inhibited the migration and invasion of bladder cancer cells through stimulating Wnt5a activation, causing the downregulation of MMP‑2 expression and enhancing the phosphorylation of JNK in these cells. However, JNK signaling did not appear to have a direct effect on the expression of MMP‑2. The present study demonstrated that 4‑HPR may be a potent anti‑invasive and anti‑metastatic agent that functions via the Wnt5a/JNK and Wnt5a/MMP-2 signaling pathways.

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