Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
1] Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China [2] Department of Urology, Jiangmen Hospital, Sun Yat-Sen University, Jiangmen, China.
Br J Cancer. 2014 Apr 2;110(7):1767-77. doi: 10.1038/bjc.2014.52. Epub 2014 Feb 6.
EIF5A2, eukaryotic translation initiation factor 5A2, is associated with several human cancers. In this study, we investigated the role of EIF5A2 in the metastatic potential of localised invasive bladder cancer (BC) and its underlying molecular mechanisms were explored.
The expression pattern of EIF5A2 in localised invasive BC was determined by immunohistochemistry. In addition, the function of EIF5A2 in BC and its underlying mechanisms were elucidated with a series of in vitro and in vivo assays.
Overexpression of EIF5A2 was an independent predictor for poor metastasis-free survival of localised invasive BC patients treated with radical cystectomy. Knockdown of EIF5A2 inhibited BC cell migratory and invasive capacities in vitro and metastatic potential in vivo and reversed epithelial-mesenchymal transition (EMT), whereas overexpression of EIF5A2 promoted BC cells motility and invasiveness in vitro and metastatic potential in vivo and induced EMT. In addition, we found that EIF5A2 might activate TGF-β1 expression to induce EMT and drive aggressiveness in BC cells. EIF5A2 stabilized STAT3 and stimulated nuclear localisation of STAT3, which resulted in increasing enrichment of STAT3 onto TGF-β1 promoter to enhance the transcription of TGF-β1.
EIF5A2 overexpression predicts tumour metastatic potential in patients with localised invasive BC treated with radical cystectomy. Furthermore, EIF5A2 elevated TGF-β1 expression through STAT3 to induce EMT and promotes aggressiveness in BC.
真核翻译起始因子 5A2（EIF5A2）与多种人类癌症有关。在这项研究中，我们研究了 EIF5A2 在局部侵袭性膀胱癌（BC）转移潜能中的作用，并探讨了其潜在的分子机制。
通过免疫组织化学检测局部侵袭性 BC 中 EIF5A2 的表达模式。此外，通过一系列体外和体内实验阐明了 EIF5A2 在 BC 中的作用及其潜在机制。
EIF5A2 的过表达是接受根治性膀胱切除术治疗的局部侵袭性 BC 患者无转移生存的独立预测因子。EIF5A2 敲低抑制了 BC 细胞的迁移和侵袭能力以及体内的转移潜能，并逆转了上皮-间充质转化（EMT），而 EIF5A2 的过表达促进了 BC 细胞的迁移和侵袭能力以及体内的转移潜能，并诱导了 EMT。此外，我们发现 EIF5A2 可能通过激活 TGF-β1 的表达来诱导 EMT 并驱动 BC 细胞的侵袭性。EIF5A2 稳定了 STAT3 并刺激了 STAT3 的核定位，导致 STAT3 更富集于 TGF-β1 启动子上，从而增强了 TGF-β1 的转录。
EIF5A2 的过表达预测了接受根治性膀胱切除术治疗的局部侵袭性 BC 患者的肿瘤转移潜能。此外，EIF5A2 通过 STAT3 升高 TGF-β1 的表达，诱导 EMT，并促进 BC 的侵袭性。
