Transforming growth factor-β1 induces glutathione peroxidase-1 and protects             from H2O2-induced cell death in colon cancer cells via the Smad2/ERK1/2/HIF-1α             pathway.
Recent studies have shown that transforming growth factor-β1 (TGF-β1) signaling             plays important roles in the redox system in benign and malignant cells. Whether             TGF-β mediates an antioxidative damage response in colorectal cancer cells is             largely unknown. Herein, using the human colorectal cancer cell lines we found             that TGF-β1 induced glutathione peroxidase-1 (GPx-1) expression and enzyme activity,             and that the upregulation of GPx-1 by TGF-β1 could protect colorectal cell lines             from H2O2-induced oxidation damage. Further, we used loss- and gain-function approaches             to elucidate the underlying mechanism and found that TGF-β1 induced GPx-1 through             activation of the TGF-β receptor type I (TGF-βRI)/Smad2/extracellular-signal-regulated             kinase 1/2 (ERK1/2)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway. This             cascade could be blocked by the TGF-βRI inhibitor or ERK1/2 inhibitor. Taken together,             our data demonstrated that TGF-β1 induced GPx-1 expression and enzymatic activity             via the TGF-βRI/Smad2/ERK1/2/HIF-1α signaling pathway, suggesting a novel antioxidative             protective function of TGF-β1 in colorectal cancer cells.
Department of Oncology, Zhongnan Hospital, Wuhan University,                     Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological                     Behaviors, Wuhan, Hubei 430071, P.R. China.
Ying
Y
Huang
Wenfeng
W
Fang
Yulei
Y
Wang
Wancai
W
Yang
Bin
B
Xiong
D000975:Antioxidants / Q000378:metabolism*; D016923:Cell Death; D045744:Cell Line, Tumor; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051899:Smad2 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D000094765:Glutathione Peroxidase GPX1
D000975:Antioxidants; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D053773:Transforming Growth Factor beta1; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human