Epithelial cell adhesion molecule overexpression regulates epithelial-mesenchymal transition, stemness and metastasis of nasopharyngeal carcinoma cells via the PTEN/AKT/mTOR pathway.
Epithelial cell adhesion molecule overexpression regulates epithelial-mesenchymal transition, stemness and metastasis of nasopharyngeal carcinoma cells via the PTEN/AKT/mTOR pathway.
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上皮细胞粘附分子过表达通过PTEN/AKT/mTOR通路调控鼻咽癌细胞上皮间质转化、干性和转移
DOI：
10.1038/s41419-017-0013-8
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发表时间：
2018-01-05
影响因子：
9
通讯作者：
Mai SJ
中科院分区：
文献类型：
--
作者：
Wang MH;Sun R;Zhou XM;Zhang MY;Lu JB;Yang Y;Zeng LS;Yang XZ;Shi L;Xiao RW;Wang HY;Mai SJ
上皮细胞粘附分子（EpCAM）在多种上皮癌中高度表达，参与细胞粘附和增殖。然而，其在鼻咽癌（NPC）中的表达谱和生物学功能尚不清楚。在这项研究中，通过qRT-PCR发现EpCAM在NPC样品中的表达高于非癌鼻咽粘膜。此外，免疫组化（IHC）分析64例鼻咽癌标本显示，高EpCAM表达与转移和生存期较短。多变量生存分析确定EpCAM高表达为独立预后因素。NPC细胞中的异位EpCAM表达促进上皮-间质转化（EMT），诱导癌症干细胞（CSC）样表型，并在体外和体内增强转移而不影响细胞增殖。值得注意的是，EpCAM过表达降低了PTEN表达，并增加了AKT、mTOR、p70 S6 K和4 EBP 1磷酸化水平。相应地，AKT抑制剂和雷帕霉素阻断了EpCAM对NPC细胞侵袭和干细胞样表型的影响，并且靶向PTEN的siRNA挽救了EpCAM敲低的NPC细胞中的致癌活性。我们的数据表明EpCAM通过PTEN/AKT/mTOR途径调节NPC细胞的EMT、干性和转移。
Epithelial cell adhesion molecule (EpCAM) is known to be highly expressed in a variety of epithelial carcinomas, and it is involved in cell adhesion and proliferation. However, its expression profile and biological function in nasopharyngeal carcinoma (NPC) remains unclear. In this study, higher expression of EpCAM was found in NPC samples compared with non-cancer nasopharyngeal mucosa by qRT-PCR. Additionally, immunohistochemistry (IHC) analysis of NPC specimens from 64 cases showed that high EpCAM expression was associated with metastasis and shorter survival. Multivariate survival analysis identified high EpCAM expression as an independent prognostic factor. Ectopic EpCAM expression in NPC cells promoted epithelial-mesenchymal transition (EMT), induced a cancer stem cell (CSC)-like phenotype, and enhanced metastasis in vitro and in vivo without an effect on cell proliferation. Notably, EpCAM overexpression reduced PTEN expression and increased the level of AKT, mTOR, p70S6K and 4EBP1 phosphorylation. Correspondingly, an AKT inhibitor and rapamycin blocked the effect of EpCAM on NPC cell invasion and stem-like phenotypes, and siRNA targeting PTEN rescued the oncogenic activities in EpCAM knockdown NPC cells. Our data demonstrate that EpCAM regulates EMT, stemness and metastasis of NPC cells via the PTEN/AKT/mTOR pathway.
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DOI：
10.1083/jcb.139.5.1337
发表时间：
1997-12-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Litvinov SV;Balzar M;Winter MJ;Bakker HA;Briaire-de Bruijn IH;Prins F;Fleuren GJ;Warnaar SO
通讯作者：
Warnaar SO
DOI：
10.1016/j.urolonc.2011.03.007
发表时间：
2013-05-01
影响因子：
2.7
作者：
Benko, Goran;Spajic, Borislav;Tomas, Davor
通讯作者：
Tomas, Davor
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
--
作者：
Liu, Ying;Chen, Long-Hua;Guan, Jian
通讯作者：
Guan, Jian
影响因子：
3.9
作者：
Ensinger, Christian;Kremser, Roswitha;Schmid, Kurt W.
通讯作者：
Schmid, Kurt W.