EIF5A2 predicts outcome in localised invasive bladder cancer and promotes bladder cancer cell aggressiveness in vitro and in vivo.

EIF5A2 predicts outcome in localised invasive bladder cancer and promotes bladder cancer cell aggressiveness in vitro and in vivo.
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EIF5A2 可预测局部浸润性膀胱癌的结果,并在体外和体内促进膀胱癌细胞的侵袭性。

DOI:
10.1038/bjc.2014.52
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发表时间:
2014-04-02
影响因子:
8.8
通讯作者:
Luo, J-H
Luo, J-H
中科院分区:
医学1区
文献类型:
--
作者:
Wei, J-H;Cao, J-Z;Zhang, D.;Liao, B.;Zhong, W-M;Lu, J.;Zhao, H-W;Zhang, J-X;Tong, Z-T;Fan, S.;Liang, C-Z;Liao, Y-B;Pang, J.;Wu, R-H;Fang, Y.;Chen, Z-H;Li, B.;Xie, D.;Chen, W.;Luo, J-H

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EIF 5A 2,真核生物翻译起始因子5A 2,与多种人类癌症相关。在这项研究中,我们研究了EIF 5A 2在局部浸润性膀胱癌(BC)转移潜力中的作用,并探讨了其潜在的分子机制。免疫组化法检测EIF 5A 2在局部浸润性BC中的表达。此外,EIF 5A 2在BC中的功能及其潜在的机制通过一系列的体外和体内测定被阐明。EIF 5A 2过表达是接受根治性化疗的局部浸润性BC患者无转移生存率差的独立预测因子。敲低EIF 5A 2可抑制BC细胞的体外迁移和侵袭能力,抑制体内转移潜能,逆转上皮-间质转化(EMT),而过表达EIF 5A 2可促进BC细胞的体外迁移和侵袭能力,促进体内转移潜能,诱导EMT。此外,我们发现EIF 5A 2可能激活TGF-β1表达以诱导EMT并驱动BC细胞的侵袭性。EIF 5A 2稳定STAT 3并刺激STAT 3的核定位,这导致STAT 3在TGF-β1启动子上的富集增加,从而增强TGF-β1的转录。EIF 5A 2过表达预测接受根治性环磷酰胺治疗的局部浸润性BC患者的肿瘤转移潜力此外,EIF 5A 2通过STAT 3升高TGF-β1表达以诱导EMT并促进BC的侵袭性。
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.
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