Department of Urology, University of Virginia, Box 800422, Charlottesville, VA 22908, USA.
Cancer Metastasis Rev. 2009 Dec;28(3-4):327-33. doi: 10.1007/s10555-009-9197-4.
Despite the recent advances in the diagnosis of bladder cancer, recurrence after surgical intervention for muscle invasive disease is still problematic as nearly half of the patients harbor occult distant metastases and this, in turn, is associated with poor 5-year survival rate. We have recently identified Rho family GDP dissociation inhibitor 2 (RhoGDI2) protein as functional metastasis suppressor and a prognostic marker in patients after cystectomy. In identifying the mechanisms underlying metastasis suppression by RhoGDI2, we found this protein to be associated with the c-Src kinase in human tumors, where the expression of both is diminished as a function of stage. Interestingly, c-Src bound to and phosphorylated RhoGDI2 resulting in enhanced metastasis suppressive potency. In this review, we will discuss the established roles of c-Src and RhoGDI2 in bladder cancer and speculate on their therapeutic relevance.
尽管近年来膀胱癌的诊断取得了进展，但手术干预肌层浸润性疾病后的复发仍然是一个问题，因为近一半的患者存在隐匿性远处转移，这反过来又与 5 年生存率差有关。我们最近发现 Rho 家族 GDP 解离抑制剂 2（RhoGDI2）蛋白作为功能性转移抑制剂，并且是膀胱切除术后患者的预后标志物。在确定 RhoGDI2 抑制转移的机制时，我们发现该蛋白与人肿瘤中的 c-Src 激酶相关，随着肿瘤分期的进展，这两种蛋白的表达均降低。有趣的是，c-Src 与 RhoGDI2 结合并使其磷酸化，从而增强了转移抑制能力。在这篇综述中，我们将讨论 c-Src 和 RhoGDI2 在膀胱癌中的既定作用，并推测它们的治疗相关性。
