RSPO3 promotes the aggressiveness of bladder cancer via Wnt/β-catenin and Hedgehog signaling pathways
RSPO3 promotes the aggressiveness of bladder cancer via Wnt/β-catenin and Hedgehog signaling pathways
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RSPO3 通过 Wnt/β-catenin 和 Hedgehog 信号通路促进膀胱癌的侵袭性
DOI：
10.1093/carcin/bgy140
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发表时间：
2019-02-01
期刊：
影响因子：
4.7
通讯作者：
Hou, Teng
中科院分区：
文献类型：
--
作者：
Chen, Zhaohui;Zhou, Lijie;Hou, Teng
R-spondin 3（RSPO 3）是一种分泌蛋白，与Wnt/β-连环蛋白信号直接相关。然而，其在人类膀胱癌中的功能贡献和预后价值仍不清楚。在此，我们发现RSPO 3在膀胱癌组织和细胞中上调，并且RSPO 3的高表达与膀胱癌患者的晚期临床病理特征、不良预后和疾病进展相关。此外，我们观察到RSPO 3的异位表达或敲低分别显著促进或抑制膀胱癌细胞的侵袭能力。从机制上讲，RSPO 3通过介导Wnt/β-连环蛋白和Hedgehog信号通路促进膀胱癌进展。这些发现首次证明，RSPO 3通过激活Wnt/β-catenin和Hedgehog信号通路在膀胱癌细胞中表现出促肿瘤作用。因此，RSPO 3可能成为膀胱癌治疗的潜在靶点。
R-spondin 3 (RSPO3) is a secreted protein that associates directly with Wnt/beta-catenin signaling. However, its functional contribution and prognostic value in human bladder cancer remain unclear. Here, we showed that RSPO3 is upregulated in bladder cancer tissues and cells, and high expression of RSPO3 correlates with advanced clinicopathological features, poor prognosis and disease progression in bladder cancer patients. Furthermore, we observed that ectopic expression or knockdown of RSPO3 profoundly promoted or inhibited, respectively, the invasive ability of bladder cancer cells. Mechanistically, RSPO3 promoted bladder cancer progression via mediating the Wnt/beta-catenin and Hedgehog signaling pathways. These findings demonstrate, for the first time, that RSPO3 exhibited a tumor-promoting effect in bladder cancer cells through activation of Wnt/beta-catenin and Hedgehog signaling pathways. Thus, RSPO3 may be served as a potential therapeutic target for bladder cancer treatment.