Abstract：
Corticotropin-releasing hormone (CRH) has been well documented playing a role in the regulation of cellular processes, immune responses, and inflammatory processes that can influence the occurrence and development of tumors. Supervillin (SVIL) is a membrane-associated and actin-binding protein, which is actively involved in the proliferation, spread, and migration of cancer cells. This work investigated CRH\'s influence on bladder cancer cells\' migration and relevant mechanisms. By using human bladder cancer cells T24 and RT4 in wound healing experiments and transwell assay, we found that the migration ability of the T24 cells was significantly increased after CRH treatment. In vivo experiments showed that CRH significantly promoted the metastases of T24 cells in cell line-derived xenograft (CDX) mouse model. Interestingly, downregulation of SVIL by SVIL-specifc small hairpin RNAs significantly reduced the promoting effect of CRH on bladder cancer cell migration. Furthermore, CRH significantly increased SVIL messenger RNA and protein expression in T24 cells, accompanied with AKT and ERK phosphorylation in T24 cells. Pretreatment with AKT inhibitor (MK2206) blocked the CRH-induced SVIL expression and ERK phosphorylation. Also, inhibition of ERK signaling pathway by U0126 significantly reduced the CRH-induced SVIL expression and AKT phosphorylation. It suggested that cross-talking between AKT and ERK pathways was involved in the effect of CRH on SVIL. Taken together, we demonstrated that CRH induced migration of bladder cancer cells, in which AKT and ERK pathways -SVIL played a key role.
摘要：
促肾上腺皮质激素释放激素（CRH）已被证明在调节细胞过程中起作用，免疫反应，和炎症过程可以影响肿瘤的发生和发展。超绒毛蛋白（SVIL）是一种膜相关和肌动蛋白结合蛋白，积极参与扩散，传播，和癌细胞的迁移。这项工作研究了CRH对膀胱癌细胞迁移的影响及其相关机制。通过使用人膀胱癌细胞T24和RT4进行伤口愈合实验和transwell测定，我们发现CRH处理后T24细胞的迁移能力显著增强。体内实验表明，CRH在细胞系来源的异种移植（CDX）小鼠模型中可明显促进T24细胞的转移。有趣的是,SVIL特异性小发夹RNA下调SVIL显著降低CRH对膀胱癌细胞迁移的促进作用。此外，CRH显著增加T24细胞中SVIL信使RNA和蛋白表达,在T24细胞中伴有AKT和ERK磷酸化。用AKT抑制剂(MK2206)预处理阻断CRH诱导的SVIL表达和ERK磷酸化。此外，U0126抑制ERK信号通路可显著降低CRH诱导的SVIL表达和AKT磷酸化。这表明AKT和ERK途径之间的交互参与了CRH对SVIL的影响。一起来看,我们证明了CRH诱导膀胱癌细胞的迁移，其中AKT和ERK通路-SVIL起关键作用。
