Risako Hiraga1, Masayoshi Kato, Shinichi Miyagawa, Tohru Kamata. 1. Department 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.
Abstract
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.
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 patienttumor 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 cancerpatients. CONCLUSIONS: These findings suggest that Nox4-derived ROS, at least in part, transmit TGF-β-triggered EMT signals through PTP1B in pancreatic cancer.
Authors: Carmen Veith; Agnes W Boots; Musa Idris; Frederik-Jan van Schooten; Albert van der Vliet Journal: Antioxid Redox Signal Date: 2019-04-05 Impact factor: 8.401
Authors: A K Thakur; J Nigri; S Lac; J Leca; C Bressy; P Berthezene; L Bartholin; P Chan; E Calvo; J L Iovanna; S Vasseur; F Guillaumond; R Tomasini Journal: Cell Death Differ Date: 2016-03-04 Impact factor: 15.828