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Updated: May 7, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Nox4-derived ROS signaling contributes to TGF-β-induced epithelial-mesenchymal transition in pancreatic cancer cells
Risako Hiraga1, Masayoshi Kato, Shinichi Miyagawa
1Department of Molecular Biology and Biochemistry, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan. kamatat@shinshu-u.ac.jp.
Unlabelled:
Transforming growth factor (TGF)-β induces epithelial-mesenchymal transition (EMT) in pancreatic adenocarcinoma. In this study, we investigated how NADPH oxidase (Nox) 4-generated reactive oxygen species (ROS) regulate TGF-β-induced EMT in pancreatic cancer cells.
Materials And Methods:
Pancreatic cancer cells were transfected with Nox4 siRNAs or PTP1B mutants and subjected to TGF-β-induced EMT assay. Expression of Nox4, TGF-β, and N-cadherin was immunohistochemically-examined with patient tumor samples.
Results:
Treatment of pancreatic cancer cells with TGF-β induced Nox4 expression, indicating that Nox4 represents a major source for ROS production. The Nox4 inhibitor diphenylene iodonium and Nox4 siRNAs blocked TGF-β-induced EMT phenotype including morphological changes, augmented migration, and altered expression of E-cadherin and Snail. Furthermore, PTP1B as a redox-sensor for Nox4-derived ROS participated in TGF-β-promoted EMT. Nox4, TGF-β, and N-cadherin were up-regulated in tumors from pancreatic cancer patients.
Conclusions:
These findings suggest that Nox4-derived ROS, at least in part, transmit TGF-β-triggered EMT signals through PTP1B in pancreatic cancer.
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