Nox4-derived ROS signaling contributes to TGF-β-induced epithelial-mesenchymal transition in pancreatic cancer cells.
2013; National Institutes of Health; Volume: 33; Issue: 10 Linguagem: Inglês
Autores
Risako Hiraga, Masayoshi Kato, Shinichi Miyagawa, Tohru Kamata,
Tópico(s)Cancer Cells and Metastasis
ResumoTransforming 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.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.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.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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