Impact of p120-catenin isoforms 1A and 3A on epithelial mesenchymal transition of lung cancer cells expressing E-cadherin in different subcellular locations.

Impact of p120-catenin isoforms 1A and 3A on epithelial mesenchymal transition of lung cancer cells expressing E-cadherin in different subcellular locations.
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p120-连环蛋白亚型1A和3A对不同亚细胞位置表达E-钙粘蛋白的肺癌细胞上皮间质转化的影响

DOI:
10.1371/journal.pone.0088064
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Wang E
Wang E
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang Y;Zhao Y;Jiang G;Zhang X;Zhao H;Wu J;Xu K;Wang E

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上皮间质转化(EMT)是肿瘤发生发展的重要过程。尽管先前的研究,仍然不清楚p120-catenin(p120 ctn)亚型1A和3A如何影响肿瘤细胞的EMT。本文应用免疫组化方法检测了78例非小细胞肺癌(NSCLC)组织中p120 ctn、E-cadherin和vimentin的表达,发现p120 ctn膜表达与E-cadherin表达呈正相关(P<0.001),与vimentin表达和淋巴结转移呈负相关(P<0.05)。p120 ctn胞浆表达与E-cadherin表达呈负相关(P<0.001),与vimentin表达及淋巴结转移呈正相关(P<0.05)。筛选高表达(H460和SPC)和低表达(H1299和LK 2)p120 ctn的细胞以研究其对EMT的影响。E-cadherin在H460和H1299细胞中定位于细胞膜,而在SPC和LK 2细胞中定位于细胞质。在表达高水平蛋白质的细胞中去除内源性p120 ctn亚型1A导致H460细胞中E-钙粘蛋白表达降低,N-钙粘蛋白、波形蛋白和snail表达增加,侵袭力增强。同时,在SPC细胞中观察到完全相反的结果。此外,用p120 ctn亚型1A质粒转染表达低p120 ctn水平的H1299细胞,导致E-钙粘蛋白表达增加,N-钙粘蛋白、波形蛋白和蜗牛表达减少,侵袭力减弱,而LK 2细胞则表现出完全相反的结果。两种表达低水平p120 ctn和转染p120 ctn亚型3A质粒的细胞系似乎具有增加的E-钙粘蛋白表达,减少的N-钙粘蛋白,波形蛋白和snail表达和减弱的侵袭性。总之,在具有膜E-钙粘蛋白的细胞中,p120 ctn亚型1A和3A均抑制EMT并降低细胞侵袭力。在细胞质E-cadherin中,p120 ctn亚型1A促进EMT,增加细胞侵袭力,而p120 ctn亚型3A抑制EMT,降低细胞侵袭力。
The epithelial mesenchymal transition (EMT) is an important process in tumor development. Despite previous investigations, it remains unclear how p120-catenin (p120ctn) isoforms 1A and 3A affect the EMT of tumor cells. Here we investigated expression of p120ctn, E-cadherin and vimentin in 78 human non-small cell lung cancer (NSCLC) samples by immunohistochemistry and found that p120ctn membrane expression positively correlated with E-cadherin expression (P<0.001) and negatively correlated with vimentin expression and lymph node metastasis (P<0.05). Meanwhile, p120ctn cytoplasmic expression negatively correlated with E-cadherin expression (P<0.001) and positively correlated with vimentin expression and lymph node metastasis (P<0.05). Cells expressing high (H460 and SPC) and low (H1299 and LK2) levels of p120ctn were screen to investigate its impact on EMT. E-cadherin was restricted to the cell membrane in H460 and H1299 cells, whereas it was expressed in the cytoplasm of SPC and LK2 cells. Ablation of endogenous p120ctn isoform 1A in cells expressing high levels of the protein resulted in decreased E-cadherin expression, increased N-cadherin, vimentin and snail expression and enhanced invasiveness in H460 cells. Meanwhile, completely opposite results were observed in SPC cells. Furthermore, transfection of in H1299 cells expressing low p120ctn levels with the p120ctn isoform 1A plasmid resulted in increased E-cadherin expression, decreased N-cadherin, vimentin and snail expression and weakened invasiveness, while LK2 cells showed completely opposite results. Both cell lines expressing low p120ctn levels and transfected with the p120ctn isoform 3A plasmid appeared to have increased E-cadherin expression, decreased N-cadherin, vimentin and snail expression and weakened invasiveness. In conclusion, in cells with membrane E-cadherin, both p120ctn isoforms 1A and 3A inhibited EMT and decreased cell invasiveness. In cells with cytoplasmic E-cadherin, p120ctn isoform 1A promoted EMT and increased cell invasiveness, while p120ctn isoform 3A inhibited the EMT and decreased cell invasiveness.
DOI: 10.1038/onc.2009.523
发表时间: 2010-04-01
期刊: ONCOGENE
影响因子: 8
作者:
Cheung, L. W. T.;Leung, P. C. K.;Wong, A. S. T.
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发表时间: 2012
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影响因子: 3.7
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DOI: 10.1091/mbc.e08-12-1196
发表时间: 2009-04-01
影响因子: 3.3
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通讯作者: Vardimon, Lily