转移，恶性肿瘤的特征之一，是导致患者死亡的最重要原因。前列腺癌是欧美国家男性发病率最高的恶性肿瘤，其致死率占肿瘤相关死亡的第二位。在我国，其发病率近年持续快速增加。然而前列腺癌发展和转移机制仍不清楚。目前已知雄激素受体（AR）在前列腺癌发展过程中具有重要作用。我们前期建立了前列腺癌骨转移和肺转移小鼠模型，获得了高器官特异性转移的细胞克隆。通过对高转移性细胞克隆与亲本细胞株进行转录组学分析，发现两种转移模型中均高表达的基因群，包括islet cell autoantigen 1（ICA1）。将该结果与临床样本的RNA芯片数据对比，显示ICA1与AR表达呈明确负相关性，并且前列腺癌及肺癌患者生存分析显示ICA1高表达的患者生存期明显缩短。为此，我们提出假说高表达ICA1下调AR的表达，促进前列腺癌细胞恶性进展和转移。研究成果将阐明新的前列腺癌恶性进展和转移的分子机制，为临床治疗提供新的靶点。

Cancer metastasis, one of the main characteristics in malignancy, contributes to high mortality in cancer patients. Prostate cancer (PCa) is the most common cancer among men and the second leading cause of cancer-related death in Europe and the United States. In China, its incidence has been dramatically increased over the past years. However, the mechanism of PCa progression and metastasis remains unclear. The androgen receptor (AR) has been demonstrated to play an important role in PCa progression and metastasis. We have previously established mouse models of PCa bone metastasis and PCa lung metastasis. We have obtained cell clones with bone-specific or lung-specific metastatic capability. By transcriptomic analysis of highly metastatic cell clones and their parental cells, we found a gene group including islet cell autoantigen 1 (ICA1) that are highly expressed in both metastatic cell clones. We further compared these results with RNA array data in clinical samples. Data comparison and correlation analysis showed that ICA1 was negatively correlated with AR expression. Survival analysis of PCa and lung cancer patients showed higher expression of ICA1 but with shorter overall survival. In this study, we propose a hypothesis that ICA1 promotes PCa progression and metastasis via AR down-regulation. Results from this project may elucidate a novel molecular mechanism of malignant progression and metastasis of PCa and thus provide new therapeutic targets.