SNAIL-MEDIATED SIGNALING IN PROSTATE CANCER

上皮-间充质转化(EMT)发生在正常胚胎发育和上皮性肿瘤期间 进步。与EMT相关的几个因素有助于运动性、侵袭性和血管生成，并可能 是前列腺癌转移的重要治疗靶点。了解影响以下因素的因素 EMT与前列腺癌转移对癌症治疗的发展至关重要。例如，Snail 转录因子被认为是在乳腺和结肠中诱导EMT的重要因素 癌症。然而，EMT在前列腺癌中的作用尚未明确，也缺乏良好的EMT模型。 最近，我们使用ARCaP细胞模型建立了前列腺癌进展的EMT模型 过度表达蜗牛。这项建议的目标是研究Snail转录因子在前列腺中的作用 癌症的进展和转移。我们发现，Snail诱导的前列腺癌细胞EMT涉及 活性氧物种(ROS)和NFDB受体激活剂(RANKL)，这两个因素在 癌症进展期和骨转移灶分别。对于这项建议，将澄清 蜗牛的生物学意义及其在骨转换中的作用。此外，我们还将描述 Snail诱导的EMT的信号通路，并最终检测拮抗Snail表达的作用 肿瘤的体外和体内侵袭性。我们相信这些研究将确定蜗牛是一个有吸引力的 治疗靶点不仅是原发肿瘤进展期间的EMT，而且还包括 辅助站点。

Epithelial-mesenchymal transition (EMT) occurs during normal embryonic development and epithelial tumor progression. Several factors associated with EMT contribute to motility, invasion, and angiogenesis, and may be important therapeutic targets for prostate cancer metastasis. Understanding the factors that contribute to EMT and prostate cancer metastasis is crucial for development of cancer therapies. For example, Snail transcription factor has been identified as an important factor that can induce EMT in breast and colon cancer. However, the role of EMT in prostate cancer is not well defined and good EMT models are lacking. Recently we have established an EMT model for prostate cancer progression using the ARCaP cell model overexpressing Snail. The goal of this proposal is to study the role of Snail transcription factor in prostate cancer progression and metastasis. We have found that Snail-induced EMT in prostate cancer cells involves reactive oxygen species (ROS) and receptor activator of NFDB (RANKL), two factors that are important in cancer disease progression and bone metastatic lesions, respectively. For this proposal, will elucidate the biological significance of Snail with emphasis of its role in bone turnover. In addition, we will characterize the signaling pathway of Snail-induced EMT, and finally examine the effect of antagonizing Snail expression on tumor aggressiveness in vitro and in vivo. We believe these studies will identify Snail as an attractive therapeutic target not only for EMT during primary tumor progression but also for bone metastatic lesions at the secondary site.