Methyl-CpG-binding domain 3 inhibits epithelial-mesenchymal transition in pancreatic cancer cells via TGF-β/Smad signalling.
Methyl-CpG-binding domain 3 inhibits epithelial-mesenchymal transition in pancreatic cancer cells via TGF-β/Smad signalling.
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甲基-CpG 结合结构域 3 通过 TGF-β/Smad 信号传导抑制胰腺癌细胞的上皮-间质转化
DOI：
10.1038/bjc.2016.397
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发表时间：
2017-01-03
影响因子：
8.8
通讯作者：
Gong A
中科院分区：
文献类型：
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作者：
Xu M;He J;Li J;Feng W;Zhou H;Wei H;Zhou M;Lu Y;Zeng J;Peng W;Du F;Gong A
甲基 CpG 结合域 3 (MBD3) 是人类恶性肿瘤中的异常表达。然而，MBD3 在胰腺癌进展中的作用仍有待阐明。在这项研究中，我们研究了 MBD3 对上皮间质转化 (EMT) 的影响，以及胰腺癌细胞中的潜在机制。通过transwell和BD Matrigel侵袭实验检测迁移和侵袭能力。对 EMT 和 TGF-β/Smad 信号传导进行了评估。首先，我们发现胰腺癌组织中MBD3的表达低于非肿瘤组织，并且MBD3水平较低的患者的存活率明显低于MBD3水平较高的患者。随后，我们发现MBD3敲低促进迁移和侵袭能力，而MBD3过表达抑制上述能力。此外，MBD3 敲除显着增加波形蛋白、α-SMA、Snail、N-钙粘蛋白、β-连环蛋白的间充质标志物表达，并下调 E-钙粘蛋白的上皮标志物表达。相反，MBD3过度表达会产生相反的效果。进一步的证据表明，MBD3 敲低会上调 TGF-β 的表达，然后激活 p-Smad2 和 p-Smad3，而 MBD3 过表达会导致 TGF-β、p-Smad2 和 p-Smad3 下调。 MBD3可能通过TGF-β/Smad信号传导抑制胰腺癌细胞中的EMT，并且可能成为胰腺癌诊断和预后的新候选靶点。
Methyl-CpG-binding domain 3 (MBD3) is an aberrant expression in human malignancies. However, the role of MBD3 in pancreatic cancer progression remains to be clarified. In this study, we investigated the effects of MBD3 on the epithelial–mesenchymal transition (EMT), and the underlying mechanism in pancreatic cancer cells. The abilities of migration and invasion were examined by transwell and BD Matrigel invasion assays. EMT and TGF-β/Smad signalling were evaluated. First, we find that MBD3 expression is lower in pancreatic cancer tissues than that in non-tumour tissues, and patients with lower MBD3 levels survive significantly less than those with higher levels. Subsequently, we find that MBD3 knockdown promotes the abilities of migration and invasion, while MBD3 overexpression inhibits the above abilities. Also, MBD3 knockdown remarkably increases mesenchymal markers expression of Vimentin, α-SMA, Snail, N-cadherin, β-catenin, and downregulates epithelial markers expression of E-cadherin. On the contrary, MBD3 overexpression results in the opposite effects. Further evidence reveals that MBD3 knockdown up-regulates expression of TGF-β, and then activates p-Smad2 and p-Smad3, while MBD3 overexpression results in downregulation of TGF-β, p-Smad2, and p-Smad3. MBD3 inhibits EMT in pancreatic cancer cells probably via TGF-β/Smad signalling, and may be a new candidate target for diagnostics and prognosis of pancreatic cancer.
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影响因子：
--
作者：
Yokoyama S;Higashi M;Kitamoto S;Oeldorf M;Knippschild U;Kornmann M;Maemura K;Kurahara H;Wiest E;Hamada T;Kitazono I;Goto Y;Tasaki T;Hiraki T;Hatanaka K;Mataki Y;Taguchi H;Hashimoto S;Batra SK;Tanimoto A;Yonezawa S;Hollingsworth MA
通讯作者：
Hollingsworth MA
影响因子：
3.7
作者：
Menafra R;Stunnenberg HG
通讯作者：
Stunnenberg HG
DOI：
10.1016/j.biocel.2010.05.006
发表时间：
2010-09-01
影响因子：
4
作者：
Lei, Weiwei;Zhang, Kehua;Song, Jianguo
通讯作者：
Song, Jianguo
影响因子：
11.2
作者：
Noh, EJ;Jang, ER;Lee, JS
通讯作者：
Lee, JS
影响因子：
4
作者：
Du L;Yamamoto S;Burnette BL;Huang D;Gao K;Jamshidi N;Kuo MD
通讯作者：
Kuo MD