deficiency of thioredoxin binding protein-2 (tbp-2) enhances tgf-β signaling and promotes epithelial to mesenchymal transition缺硫氧还蛋白绑定protein-2(tbp-2)增强tgf-β信号,促进上皮间充质转变.pdfVIP

Deficiency of Thioredoxin Binding Protein-2 (TBP-2) Enhances TGF-b Signaling and Promotes Epithelial to Mesenchymal Transition 1 1 1 1,2 So Masaki , Hiroshi Masutani , Eiji Yoshihara , Junji Yodoi * 1 Laboratory of Infection and Prevention, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan, 2 Department of Bioinspired Sciences, Center for Cell Signaling Research, Ewha Womans University, Seoul, South Korea Abstract Background: Transforming growth factor beta (TGF- b) has critical roles in regulating cell growth, differentiation, apoptosis, invasion and epithelial-mesenchymal transition (EMT) of various cancer cells. TGF-b-induced EMT is an important step during carcinoma progression to invasion state. Thioredoxin binding protein-2 (TBP-2, also called Txnip or VDUP1) is downregulated in various types of human cancer, and its deficiency results in the earlier onset of cancer. However, it remains unclear how TBP-2 suppresses the invasion and metastasis of cancer. Principal Findings: In this study, we demonstrated that TBP-2 deficiency increases the transcriptional activity in response to TGF- b and also enhances TGF-b-induced Smad2 phosphorylation levels. Knockdown of TBP-2 augmented the TGF-b- responsive expression of Snail and Slug, transcriptional factors related to TGF-b-mediated induction of EMT, and promoted TGF- b-induced spindle-like morphology consistent with the depletion of E-Cadherin in A549 cells. Conclusions/Significance: Our results indicate that TBP-2 deficiency enhances TGF-b signaling and promotes TGF-b- induced EMT. The control of TGF-b-induced EMT is critical for the inhibition of the invasion and metastasis.