Research for a mechanism of urologic cancer metastasis through a GAP signaling pathway

侵袭性膀胱癌细胞中，由于RalGAPa2的表达减少，Ral被高度激活。在侵袭型膀胱癌细胞中外源表达RalGAPa2可导致细胞体外迁移减弱和体内肺转移。在化学诱导的小鼠膀胱癌模型中，基因消融Ralgapa2促进肿瘤侵袭。对膀胱癌标本进行免疫组化分析发现，RalGAPa2的低表达与患者临床分期较晚、生存期较差有关。总之，这些结果高度表明RalGAPa2的表达减弱通过增强Ral活性导致膀胱癌的疾病进展。

Ral was highly activated in invasive bladder cancer cells due to reduced expression of RalGAPa2. Exogenous expression of RalGAPa2 in bladder cancer cells with invasive phenotype resulted in attenuated cell migration in vitro and lung metastasis in vivo. Genetic ablation of Ralgapa2 promoted tumor invasion in a chemically-induced murine bladder cancer model. Immunohistochemical analysis of human bladder cancer specimens revealed that lower expression of RalGAPa2 was associated with advanced clinical stage and poor survival of patients. Collectively, these results are highly indicative that attenuated expression of RalGAPa2 leads to disease progression of bladder cancer through enhancement of Ral activity.