SNAIL-MEDIATED SIGNALING IN HUMAN PROSTATE CANCER

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 上皮间质转化（EMT）发生在正常胚胎发育和上皮肿瘤进展过程中。与 EMT 相关的几个因素有助于运动、侵袭和血管生成，并且可能是前列腺癌转移的重要治疗靶点。了解导致 EMT 和前列腺癌转移的因素对于癌症疗法的开发至关重要。例如，Snail转录因子已被确定为可诱导乳腺癌和结肠癌EMT的重要因子。 然而，EMT 在前列腺癌中的作用尚不明确，也缺乏良好的 EMT 模型。最近，我们使用过表达 Snail 的 ARCaP 细胞模型建立了前列腺癌进展的 EMT 模型。该提案的目标是研究 Snail 转录因子在前列腺癌进展和转移中的作用。我们发现，Snail 在前列腺癌细胞中诱导的 EMT 涉及活性氧 (ROS) 和 NFkB 受体激活剂 (RANKL)，这两个因素分别在癌症疾病进展和骨转移病变中发挥重要作用。该提案将阐明 Snail 的生物学意义，重点是其在前列腺癌骨转移中的作用。此外，我们将表征Snail诱导EMT的信号通路，并最终检查拮抗Snail表达对体外和体内肿瘤侵袭性的影响。我们相信，这些研究将确定 Snail 不仅是原发性肿瘤进展期间 EMT 的一个有吸引力的治疗靶点，而且也是继发部位骨转移病变的一个有吸引力的治疗靶点。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 NFkB (RANKL), two factors that are important in cancer disease progression and bone metastatic lesions, respectively. This proposal will elucidate the biological significance of Snail, with emphasis of its role in prostate cancer bone metastasis. 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.