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SSH1 在结直肠癌预后和肿瘤进展中的作用。

Role of SSH1 in colorectal cancer prognosis and tumor progression.

机构信息

Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China.

Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.

出版信息

J Gastroenterol Hepatol. 2020 Jul;35(7):1180-1188. doi: 10.1111/jgh.15001. Epub 2020 Feb 14.

Abstract

BACKGROUND AND AIM

Slingshot 1 protein (SSH1) plays a critical role in cytoskeleton dynamic regulation. Increasing evidence suggest that SSH1 expression is upregulated in several cancers and relates to tumor progression and drug resistance. Here, we evaluated the role of SSH1 in colorectal cancer (CRC) development and its prognostic value in patients with CRC.

METHODS

SSH1 expression was examined by quantitative real-time polymerase chain reaction, western blot analysis, or immunohistochemistry. The association between SSH1 expression and clinical characteristics and prognosis was evaluated. Stable SSH1 knockdown cells were used for in vitro assays and xenograft models. Correlation between SSH1 expression and epithelial-mesenchymal transition (EMT) was analyzed by western blot and online data analysis.

RESULTS

SSH1 expression was upregulated in cancer tissue compared with paired non-cancerous tissue in patients with CRC. SSH1 expression level in CRC tissue was associated with tumor stage, lymph node metastasis, and correlated with poor prognosis as indicated by univariate and multivariate analyses. In vitro, loss of SSH1 impaired colony formation, migration, and invasion of CRC cells. In vivo data suggest that SSH1 could promote the progression and metastasis of CRC. Interestingly, E-cadherin, ZEB1, and Snail, which are markers of EMT, had a significant expression correlation with SSH1.

CONCLUSIONS

SSH1 expression is associated with CRC progression and predicts poor prognosis. SSH1 may promote CRC tumor progression by regulating EMT.

摘要

背景与目的

弹弓 1 蛋白(SSH1)在细胞骨架动态调节中起着关键作用。越来越多的证据表明,SSH1 的表达在几种癌症中上调,并与肿瘤进展和耐药性有关。在这里,我们评估了 SSH1 在结直肠癌(CRC)发展中的作用及其在 CRC 患者中的预后价值。

方法

通过实时定量聚合酶链反应、western blot 分析或免疫组织化学检测 SSH1 表达。评估 SSH1 表达与临床特征和预后的关系。使用稳定的 SSH1 敲低细胞进行体外测定和异种移植模型。通过 western blot 和在线数据分析分析 SSH1 表达与上皮-间充质转化(EMT)的相关性。

结果

与 CRC 患者配对的非癌组织相比,癌症组织中 SSH1 的表达上调。CRC 组织中 SSH1 的表达水平与肿瘤分期、淋巴结转移有关,并通过单因素和多因素分析与预后不良相关。体外实验表明,SSH1 的缺失削弱了 CRC 细胞的集落形成、迁移和侵袭能力。体内数据表明,SSH1 可促进 CRC 的进展和转移。有趣的是,上皮-间充质转化(EMT)的标志物 E-钙黏蛋白、ZEB1 和 Snail 与 SSH1 具有显著的表达相关性。

结论

SSH1 的表达与 CRC 的进展相关,并预测预后不良。SSH1 可能通过调节 EMT 促进 CRC 肿瘤的进展。

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