Wnt5a signaling is involved in the aggressiveness of prostate cancer and expression of metalloproteinase
Wnt5a signaling is involved in the aggressiveness of prostate cancer and expression of metalloproteinase
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DOI：
10.1038/onc.2009.496
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发表时间：
2010-04-08
期刊：
影响因子：
8
通讯作者：
Kikuchi, A.
中科院分区：
文献类型：
--
作者：
Yamamoto, H.;Oue, N.;Kikuchi, A.
Wnt5a是激活Wnt信号中β -catenin-independent通路的代表性配体。尽管有报道称在人类前列腺癌中经常观察到Wnt/ β -catenin依赖性通路的异常激活，但b-catenin非依赖性通路在这种癌症中的作用尚不清楚。免疫组化分析98例前列腺癌患者中，Wnt5a和β -catenin分别有27例（28%）和49例（50%）表达异常。Wnt5a和b-catenin同时表达的病例仅有5例，提示它们是排他表达的。Wnt5a阳性检测与高Gleason评分及前列腺癌生化复发相关，而b-catenin阳性检测与高Gleason评分及前列腺癌生化复发无关。在人前列腺癌细胞系中，Wnt5a的敲低和过表达分别降低和刺激其侵袭活性，其侵袭活性需要Frizzled2和Ror2作为Wnt受体。Wnt5a通过蛋白激酶D （PKD）激活jun - n-末端激酶，抑制PKD可抑制Wnt5a依赖性细胞的迁移和侵袭。此外，Wnt5a通过将JunD募集到其启动子区域来诱导金属蛋白酶-1的表达。这些结果表明，Wnt5a促进前列腺癌的侵袭性，其表达参与前列腺切除术后的复发。中国癌症杂志（2010）29,2036-2046；doi: 10.1038 / onc.2009.496;2010年1月18日在线发布
Wnt5a is a representative ligand that activates the beta-catenin-independent pathway in Wnt signaling. Although it has been reported that abnormal activation of the Wnt/beta-catenin-dependent pathway is often observed in human prostate cancer, the involvement of the b-catenin-independent pathway in this cancer is unclear. Abnormal expression of Wnt5a and beta-catenin was observed in 27 (28%) and 49 (50%) of 98 prostate cancer cases, respectively, by immunohistochemical analyses. Simultaneous expression of Wnt5a and b-catenin was observed in only five cases, suggesting their exclusive expression. The positive detection of Wnt5a was correlated with high Gleason scores and biochemical relapse of prostate cancer, but that of b-catenin was not. Knockdown and overexpression of Wnt5a in human prostate cancer cell lines reduced and stimulated, respectively, their invasion activities, and the invasion activity required Frizzled2 and Ror2 as Wnt receptors. Wnt5a activated Jun-N-terminal kinase through protein kinase D (PKD) and the inhibition of PKD suppressed Wnt5a-dependent cell migration and invasion. In addition, Wnt5a induced the expression of metalloproteinase-1 through the recruitment of JunD to its promoter region. These results suggest that Wnt5a promotes the aggressiveness of prostate cancer and that its expression is involved in relapse after prostatectomy. Oncogene (2010) 29, 2036-2046; doi: 10.1038/onc.2009.496; published online 18 January 2010