Investigating the Interplay Between WNT and FGF Signaling in Prostate Initiation

描述(申请人提供)：本研究的长期目标是了解前列腺形成和维持的分子机制。前列腺一直是密集的生物医学研究的主题，不仅是因为它在性功能中的关键作用，更是因为人类前列腺疾病的高发病率。尽管做出了努力，但仍有一个方面仍然知之甚少，那就是前列腺启动的分子机制，这也是拟议中的研究的重点。到目前为止，除了雄激素途径外，只有一条信号通路，即成纤维细胞生长因子(成纤维细胞生长因子)途径，在遗传学上被证明是所有前列腺芽启动所必需的。在这项提案中，我们提供了初步数据，表明WNT信号对前列腺癌的启动是必不可少的。根据我们最近在肺中的发现，我们假设WNT在前列腺启动中的作用是通过其对成纤维细胞生长因子信号的调节来实现的。我们将使用先进的遗传方法来解决这两个信号通路之间的关系，这是前列腺发育的关键第一步。这项提议定义了一项长期战略的开始，该战略旨在剖析对前列腺发育和动态平衡至关重要的信号网络。与公共健康相关：这项提案旨在定义WNT和成纤维细胞生长因子信号如何共同作用来控制前列腺的形成。由于这两条途径都是干细胞维持和前列腺癌发生的中心，我们的发现将为未来研究它们在前列腺癌发病机制中的相互作用提供基础。

DESCRIPTION (provided by applicant): The long-term objective of this study is to understand the molecular mechanism of prostate formation and maintenance. The prostate has been the subject of intense biomedical research not only because of its key role in sexual function, but more because of the high incidence of human prostate diseases. Despite the effort, one aspect that has remained poorly understood is the molecular mechanism of prostate initiation, and this is the focus of the proposed study. To date, in addition to the androgen pathway, only one signaling pathway, the Fibroblast Growth Factor (FGF) pathway has been genetically demonstrated to be essential for the initiation of all prostate buds. In this proposal, we present preliminary data suggesting that WNT signaling is essential for prostate initiation. Drawing from our recent findings in the lung, a similar branching organ as the prostate, we hypothesize that WNT function in prostate initiation is mediated through its regulation of FGF signaling. We will use advanced genetic approaches to address the relationship between these two signaling pathways in this essential first step of prostate development. This proposal defines the beginning of a long-term strategy to dissect the signaling network essential for the development and homeostasis of the prostate. PUBLIC HEALTH RELEVANCE: This proposal aims to define how WNT and FGF signaling function together to control prostate formation. As both pathways are central to stem cell maintenance and prostate tumorigenesis, our finding will provide the basis for future investigation of their interaction in prostate pathogenesis.