Trim28 contributes to EMT via regulation of E-cadherin and N-cadherin in lung cancer cell lines.
Trim28 contributes to EMT via regulation of E-cadherin and N-cadherin in lung cancer cell lines.
复制标题
DOI：
10.1371/journal.pone.0101040
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Cress WD
中科院分区：
文献类型：
--
作者：
Chen L;Muñoz-Antonia T;Cress WD
在之前的工作中，我们证明转录因子Trim28 （Tripartite motif containing 28）在早期肺腺癌中发挥肿瘤抑制作用，因为它能够抑制细胞周期调节基因的转录。在这里，我们研究了Trim28在上皮到间质转化（EMT）中的作用，这与癌症转移密切相关。我们发现Trim28在TGF-β诱导的非小细胞肺癌细胞EMT中发挥作用。用抑制性rna沉默Trim28会改变许多EMT标记物的表达，如E-cadherin和N-cadherin，而过表达Trim28则会产生相反的效果。TGF-β处理可诱导Trim28蛋白和mRNA水平的表达。Trim28缺乏损害TGF-β诱导的EMT，降低细胞迁移和侵袭。最后，我们证明了Trim28的表达影响E-cadherin和N-cadherin启动子上组蛋白的乙酰化和甲基化。这些结果表明Trim28参与了EMT，可能在肺癌的肿瘤转移中起重要作用。结合我们之前的工作，这些结果表明Trim28在肺癌转化过程的早期是肿瘤抑制因子，但在后期它作为癌基因发挥作用。
In previous work, we demonstrated that transcription factor Trim28 (Tripartite motif containing 28) plays a tumor-suppressor role in early-staged adenocarcinoma of the lung due to its ability to restrain transcription of cell cycle-regulating genes. Herein we examine Trim28's role in the epithelial-to-mesenchymal transition (EMT) which is strongly implicated in cancer metastasis. We found that Trim28 plays a role in TGF-β-induced EMT in non-small cell lung cancer cells. Silencing Trim28 with inhibitory RNAs alters the expression of numerous EMT markers, such as E-cadherin and N-cadherin, whereas overexpression of Trim28 has an opposite effect. Trim28 expression is induced following TGF-β treatment at both protein and mRNA levels. Trim28 deficiency impairs TGF-β-induced EMT and decreases cell migration and invasion. Finally, we demonstrate that the expression of Trim28 affects the acetylation and methylation of histones on E-cadherin and N-cadherin promoters. These results suggest that Trim28 contributes to EMT and might be important for tumor metastasis in lung cancer. Taken together with our previous work these results suggest a model in which Trim28 is a tumor suppressor early in the transformation process in lung cancer, but in later stages it functions as an oncogene.
登录
查看更多内容
影响因子：
3.7
作者：
Kumar M;Allison DF;Baranova NN;Wamsley JJ;Katz AJ;Bekiranov S;Jones DR;Mayo MW
通讯作者：
Mayo MW
DOI：
10.1073/pnas.0907601107
发表时间：
2010-06-15
影响因子：
11.1
作者：
Seki, Yasuhiro;Kurisaki, Akira;Asashima, Makoto
通讯作者：
Asashima, Makoto
影响因子：
10.5
作者：
Friedman, JR;Fredericks, WJ;Rauscher, FJ
通讯作者：
Rauscher, FJ
影响因子：
11.2
作者：
Javelaud D;Alexaki VI;Dennler S;Mohammad KS;Guise TA;Mauviel A
通讯作者：
Mauviel A
影响因子：
82.9
作者：
Beer, DG;Kardia, SLR;Hanash, S
通讯作者：
Hanash, S