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

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

  • Oncogenesis. 2020 Aug 26;9(8):76. doi: 10.1038/s41389-020-00258-y.
Huizhi Wang  # 1,  Jie Li  # 1 2,  Junbo He  # 1,  Yawen Liu 1,  Wen Feng 1,  Hailang Zhou 1,  Meng Zhou 1,  Hong Wei 1,  Ying Lu 1,  Wanxin Peng 3,  Fengyi Du 3,  Aihua Gong 4,  Min Xu 5
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, 438 Jiefang Road, Zhenjiang, 212000, China.
  • 2 Department of Gastroenterology, The First People's Hospital of Jingzhou, 8 Aviation Road, Jingzhou, 434000, China.
  • 3 Department of Cell Biology, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212000, China.
  • 4 Department of Cell Biology, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212000, China. ahg5@mail.ujs.edu.cn.
  • 5 Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, 438 Jiefang Road, Zhenjiang, 212000, China. peterxu1974@163.com.
  • # Contributed equally.
PMID: 32848128 DOI: 10.1038/s41389-020-00258-y
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.

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