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星形胶质细胞上调基因-1通过诱导口腔鳞状细胞癌的上皮-间质转化促进肿瘤生长和侵袭。

Astrocyte elevated gene-1 promotes tumour growth and invasion by inducing EMT in oral squamous cell carcinoma.

作者信息

Wang Yan, Wang Ting, Sun Yunduan, Sun Wenjing, Wang Xiumei

机构信息

Department of Dentistry, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.

Department of Ophthalmology, the First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.

出版信息

Sci Rep. 2017 Nov 13;7(1):15447. doi: 10.1038/s41598-017-15805-8.

Abstract

Oral squamous cell carcinoma (OSCC) is a common human malignancy with a high incidence rate and poor prognosis. Although astrocyte elevated gene 1 (AEG-1) expression is up-regulated in various human cancers and plays an important role in carcinogenesis and tumour progression, the impact of AEG-1 on the development and progression of OSCC remains unclear. Accordingly, this study aims to clarify the biological significance of AEG-1 in OSCC. We found AEG-1 to be overexpressed in OSCC tissues compared to normal oral mucosa. Knockdown or overexpression of AEG-1 in OSCC cell lines showed that AEG-1 is important for tumour growth, apoptosis, drug tolerance, and maintaining epithelial-mesenchymal transition (EMT)-mediated cell migration and invasion in vitro. Moreover, in a xenograft-mouse model generated by AEG-1-overexpressing SCC15 cells, we found that higher expression of AEG-1 promoted tumour growth, angiogenesis, and EMT in vivo. These findings provide mechanistic insight into the role of AEG-1 in regulating OSCC tumour growth, apoptosis, drug tolerance, and invasion, as well as AEG-1-induced activation of p38 and NF-κB signalling, suggesting that AEG-1 is an important prognostic factor and therapeutic target for OSCC.

摘要

口腔鳞状细胞癌(OSCC)是一种常见的人类恶性肿瘤,发病率高且预后较差。尽管星形胶质细胞上调基因1(AEG-1)在多种人类癌症中表达上调,并在致癌作用和肿瘤进展中发挥重要作用,但AEG-1对OSCC发生发展的影响仍不清楚。因此,本研究旨在阐明AEG-1在OSCC中的生物学意义。我们发现,与正常口腔黏膜相比,AEG-1在OSCC组织中过表达。在OSCC细胞系中敲低或过表达AEG-1表明,AEG-1对肿瘤生长、凋亡、药物耐受性以及维持上皮-间质转化(EMT)介导的体外细胞迁移和侵袭很重要。此外,在由过表达AEG-1的SCC15细胞生成的异种移植小鼠模型中,我们发现AEG-1的高表达在体内促进了肿瘤生长、血管生成和EMT。这些发现为AEG-1在调节OSCC肿瘤生长、凋亡、药物耐受性和侵袭中的作用提供了机制性见解,以及AEG-1诱导的p38和NF-κB信号通路激活,表明AEG-1是OSCC的一个重要预后因素和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/643f/5684276/9ce0687b35ef/41598_2017_15805_Fig1_HTML.jpg

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