title: Deficiency of thioredoxin binding protein-2 (TBP-2) enhances TGF-β signaling and promotes epithelial to mesenchymal transition.
abstract: BACKGROUND
  Transforming growth factor beta (TGF-β) has critical roles in regulating cell growth, differentiation, apoptosis, invasion and epithelial-mesenchymal transition (EMT) of various cancer cells. TGF-β-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.
  
  
  RESULTS
  In this study, we demonstrated that TBP-2 deficiency increases the transcriptional activity in response to TGF-β and also enhances TGF-β-induced Smad2 phosphorylation levels. Knockdown of TBP-2 augmented the TGF-β-responsive expression of Snail and Slug, transcriptional factors related to TGF-β-mediated induction of EMT, and promoted TGF-β-induced spindle-like morphology consistent with the depletion of E-Cadherin in A549 cells.
  
  
  CONCLUSIONS
  Our results indicate that TBP-2 deficiency enhances TGF-β signaling and promotes TGF-β-induced EMT. The control of TGF-β-induced EMT is critical for the inhibition of the invasion and metastasis. Thus TBP-2, as a novel regulatory molecule of TGF-β signaling, is likely to be a prognostic indicator or a potential therapeutic target for preventing tumor progression.
authors: Laboratory of Infection and Prevention, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors: So
authors: S
authors: Masaki
authors: Hiroshi
authors: H
authors: Masutani
authors: Eiji
authors: E
authors: Yoshihara
authors: Junji
authors: J
authors: Yodoi
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D048430:Cell Shape / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051899:Smad2 Protein / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D013879:Thioredoxins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D015820:Cadherins; D002352:Carrier Proteins; D012333:RNA, Messenger; C000604407:SNAI1 protein, human; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; C486715:TXNIP protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C445672:Txnip protein, mouse; D013879:Thioredoxins