Robinson Daniel R, Zylstra Cassandra R, Williams Bart O
Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, 333 Bostwick NE, Grand Rapids, MI 49503, USA.
Curr Drug Targets. 2008 Jul;9(7):571-80. doi: 10.2174/138945008784911831.
Canonical Wnt signaling has emerged as an important pathway that underlies the initia nottion of prostate cancer. Both human cancers and mouse models have confirmed that mutations or altered expression of components of this pathway are associated with prostate tumors. Additionally, several reports suggest that this pathway plays a key role in the establishment of skeletal metastasis. This review discusses our current knowledge of the Wnt signaling pathway in the development of prostate cancer. First, we will overview the Wnt signaling pathway to provide background for the rest of the discussion. We will then review the literature on the role of this pathway and the down notstream effector, beta-catenin, in the development and progression of prostate cancer and skeletal metastasis. We will also discuss reports that suggest that beta-catenin can directly interact with the androgen receptor to modulate its activity. These recent developments may provide insight into how tumor growth can be achieved under androgen deprivation. Finally, we speculate on how the pathway may be targeted for therapeutic treatment and what agents may be available to achieve this goal.
经典Wnt信号通路已成为前列腺癌起始的重要通路。人类癌症和小鼠模型均已证实，该通路成分的突变或表达改变与前列腺肿瘤相关。此外，一些报告表明，该通路在骨转移的形成中起关键作用。本综述讨论了我们目前对Wnt信号通路在前列腺癌发展中的认识。首先，我们将概述Wnt信号通路，为其余讨论提供背景。然后，我们将回顾关于该通路及其下游效应物β-连环蛋白在前列腺癌发展和进展以及骨转移中的作用的文献。我们还将讨论表明β-连环蛋白可直接与雄激素受体相互作用以调节其活性的数据。这些最新进展可能为雄激素剥夺条件下如何实现肿瘤生长提供见解。最后，我们推测该通路如何可能成为治疗靶点以及哪些药物可用于实现这一目标。
