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

在浸润性膀胱癌细胞中，由于RalGAPa2的表达减少，RAL被高度激活。外源性RalGAPa2在侵袭表型的膀胱癌细胞中的表达可导致体外细胞迁移减弱和体内肺转移减少。在化学诱导的小鼠膀胱癌模型中，Ralgapa2的基因消融促进了肿瘤的侵袭。免疫组织化学分析表明，RalGAPa2的低表达与膀胱癌的临床分期和患者的生存不良有关。总而言之，这些结果高度表明，RalGAPa2的减弱表达通过增强Ral的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.