Epidermal growth factor receptor kinase substrate 8 promotes the metastasis of cervical cancer via the epithelial-mesenchymal transition.
Epidermal growth factor receptor kinase substrate 8 promotes the metastasis of cervical cancer via the epithelial-mesenchymal transition.
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表皮生长因子受体激酶底物8通过上皮间质转化促进宫颈癌转移
DOI：
10.3892/mmr.2016.5638
复制
发表时间：
2016-10
影响因子：
3.4
通讯作者：
Wu D
中科院分区：
文献类型：
--
作者：
Li Q;Bao W;Fan Q;Shi WJ;Li ZN;Xu Y;Wu D
表皮生长因子受体途径底物8（Eps 8）已被鉴定为表皮生长因子受体（EGFR）激酶的新型底物，并且参与EGFR介导的与多种癌症类型中的肿瘤发生、增殖和转移相关的信号传导途径。然而，Eps 8在宫颈癌转移中的确切作用仍有待阐明。免疫组化结果显示，Eps 8在宫颈癌组织中的表达明显高于正常宫颈组织和鳞状上皮内病变组织。此外，还发现Eps 8表达不仅与宫颈癌进展相关，而且与上皮-间质转化（EMT）标志物E-cadherin和vimentin密切相关。此外，本研究主要集中在EMT相关的作用Eps 8在子宫颈癌细胞的EMT，迁移和侵袭。将Eps 8-短发夹RNA转染HeLa和SiHa细胞，使其表达缺失，通过逆转录-定量聚合酶链反应和蛋白质印迹分析证实Eps 8-敲低，并研究Eps 8对EMT标志物的影响。目前的研究结果表明，Eps 8沉默导致上皮标志物E-钙粘蛋白的上调，而间充质标志物波形蛋白和转录因子snail的表达在mRNA和蛋白质表达水平上均降低。Transwell细胞迁移和Matrigel侵袭实验表明，下调Eps 8表达可显著抑制HeLa和SiHa细胞的迁移和侵袭。总之，这些结果表明Eps 8通过协调EMT促进宫颈癌转移。
Epidermal growth factor receptor pathway substrate 8 (Eps8) has been identified as a novel substrate for epidermal growth factor receptor (EGFR) kinase and is involved in EGFR-mediated signaling pathways correlated with tumorigenesis, proliferation and metastasis in various cancer types. However, the precise role of Eps8 in cervical cancer metastasis remains to be elucidated. Immunohistochemistry revealed that Eps8 was significantly increased in cervical cancer specimens compared with squamous intraepithelial lesion and normal cervical tissues. Additionally, it was revealed that Eps8 expression not only correlated with cervical cancer progression, but also exhibited a close correlation with the epithelial-mesenchymal transition (EMT) markers, E-cadherin and vimentin. Furthermore, the present study focused predominantly on the EMT-associated role of Eps8 in the EMT, migration and invasion of cervical cancer cells. Eps8-short hairpin (sh) RNA was transfected into HeLa and SiHa cells to deplete its expression, and reverse transcription-quantitative polymerase chain reaction and western blot analyses were performed to confirm Eps8-knockdown and to investigate the influence of Eps8 on EMT markers. The present findings have revealed that Eps8 silencing led to the upregulation of the epithelial marker E-cadherin, while expression of the mesenchymal marker vimentin and the transcription factor snail was decreased at both mRNA and protein expression levels. Transwell cell migration and Matrigel invasion assays showed that downregulation of Eps8 significantly inhibited cell migration and invasion of HeLa and SiHa cells. Taken together, these results suggested that Eps8 promotes cervical cancer metastasis by orchestrating the EMT.
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DOI：
10.1016/j.biocel.2007.07.011
发表时间：
2007-01-01
影响因子：
4
作者：
Guarino, Marcello
通讯作者：
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影响因子：
20.3
作者：
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DOI：
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发表时间：
2015-03-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
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作者：
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影响因子：
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DOI：
10.1083/jcb.200206079
发表时间：
2003-01-06
期刊：
The Journal of cell biology
影响因子：
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作者：
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Scita G