Wnt signaling in ovarian tumorigenesis
Wnt signaling in ovarian tumorigenesis
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DOI：
10.1111/j.1525-1438.2007.01127.x
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发表时间：
2008-09-01
影响因子：
4.8
通讯作者：
Holcombe, R. F.
中科院分区：
文献类型：
--
作者：
Gatcliffe, T. A.;Monk, B. J.;Holcombe, R. F.
越来越多的数据表明Wnt信号与卵巢肿瘤的发生有关。我们试图回顾当前关于这一主题的文献，并讨论该通路作为预后标记物和治疗靶点的潜在作用。我们对研究Wnt信号与卵巢癌之间关系的研究进行了系统的文献综述。搜索策略包括在线搜索MEDLINE数据库和手工搜索相关出版物和评论。通过系统地审查检索到的论文中的所有参考文献，收集了其他报告。确定了29篇直接研究Wnt信号与卵巢癌的文章。CTNNB1基因编码β-连环蛋白，是该途径中的关键效应因子，它的突变与致癌转化直接相关，但主要在卵巢子宫内膜样腺癌中发现，卵巢子宫内膜样腺癌是卵巢上皮癌的一种组织学亚型。这些突变与其他突变一起，导致该途径的失控和靶基因的转录。Wnt途径的各种细胞内外成分在正常卵巢和癌细胞系以及良性组织和卵巢癌之间的差异已被证明。这些差异表明Wnt信号与导致卵巢癌发生的分子事件有关，尽管基因突变并不常见。这些数据表明Wnt信号在卵巢肿瘤的发生中起作用。发生这种情况的确切机制需要进一步阐明。WNT信号可能通过多种不同的机制参与其中。这方面的进一步研究是有必要的。
Data are emerging implicating Wnt signaling in ovarian tumorigenesis. We sought to review the current literature on the subject and discuss the pathway's potential role as a prognostic marker and therapeutic target. We conducted a systematic literature review of studies investigating the association between Wnt signaling and ovarian cancer. Search strategies included online searching of the MEDLINE database and hand searching of relevant publications and reviews. Additional reports were collected by systematically reviewing all references from retrieved papers. Twenty-nine papers were identified that directly investigate Wnt signaling and ovarian cancer. Mutations in the CTNNB1 gene that codes for beta-catenin, the key effector in the pathway, are directly linked to carcinogenic transformation but are mostly found in ovarian endometrioid adenocarcinomas, a histologic subtype of epithelial ovarian cancer. These mutations, along with others, lead to deregulation of the pathway and transcription of target genes. Differences in various intra- and extracellular components of the Wnt pathway have been demonstrated between normal ovarian and cancer cell lines and between benign tissue and ovarian cancer. These differences implicate Wnt signaling in the molecular events that lead to ovarian cancer development despite the fact that gene mutations are uncommon. The data suggest that Wnt signaling plays a role in ovarian tumorigenesis. The exact mechanisms by which this occurs need to be further elucidated. Wnt signaling is probably involved via multiple, diverse mechanisms. Further research in this area is warranted.