Methyl-CpG-binding protein 2 drives the Furin/TGF-β1/Smad axis to promote epithelial–mesenchymal transition in pancreatic cancer cells

Abstract Methyl-CpG-binding protein 2 (MeCP2) has been characterized as an oncogene in several types of cancer. However, its precise role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. Hence, this study aimed to evaluate the potential role of MeCP2 in pancreatic cancer progression. We f...

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Published in:Oncogenesis (New York, NY) NY), 2020-08, Vol.9 (8), p.76-76, Article 76
Main Authors: Wang, Huizhi, Li, Jie, He, Junbo, Liu, Yawen, Feng, Wen, Zhou, Hailang, Zhou, Meng, Wei, Hong, Lu, Ying, Peng, Wanxin, Du, Fengyi, Gong, Aihua, Xu, Min
Format: Article
Language:English
Subjects:
Adenocarcinoma
Cell proliferation
E-cadherin
Furin
MeCP2 protein
Mesenchyme
Methyl-CpG binding protein
N-Cadherin
Pancreatic cancer
Smad protein
Smad2 protein
Smad3 protein
Transcription
Transforming growth factor-b1
Tumorigenesis
Vimentin
Zonula occludens-1 protein
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Summary:Abstract Methyl-CpG-binding protein 2 (MeCP2) has been characterized as an oncogene in several types of cancer. However, its precise role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. Hence, this study aimed to evaluate the potential role of MeCP2 in pancreatic cancer progression. We found that MeCP2 was upregulated in pancreatic cancer tissues, enhanced migration, invasion, and proliferation in pancreatic cancer cells, and promoted tumorigenesis. Further evidence revealed that MeCP2 remarkably increased the mesenchymal markers vimentin, N-cadherin, and Snail, and downregulated the expression of the epithelial markers E-cadherin and ZO-1, indicating that MeCP2 promotes epithelial–mesenchymal transition (EMT). In addition, we found that MeCP2 upregulated the expression of Furin, activated TGF-β1, and increased the levels of p-Smad2/3. Importantly, we demonstrated that MeCP2, as a coactivator, enhanced Smad3 binding to the furin promoter to improve its transcription. Therefore, MeCP2/Smads drive the expression of Furin to activate TGF-β1, and in turn, phosphorylate Smad2/3, which forms a positive-feedback axis to promote EMT in pancreatic cancer cells.
ISSN:2157-9024
2157-9024
DOI:10.1038/s41389-020-00258-y