Dataset Information

Deficiency of thioredoxin binding protein-2 (TBP-2) enhances TGF-? signaling and promotes epithelial to mesenchymal transition.

ABSTRACT:

Background

Transforming growth factor beta (TGF-?) has critical roles in regulating cell growth, differentiation, apoptosis, invasion and epithelial-mesenchymal transition (EMT) of various cancer cells. TGF-?-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-? and also enhances TGF-?-induced Smad2 phosphorylation levels. Knockdown of TBP-2 augmented the TGF-?-responsive expression of Snail and Slug, transcriptional factors related to TGF-?-mediated induction of EMT, and promoted TGF-?-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-? signaling and promotes TGF-?-induced EMT. The control of TGF-?-induced EMT is critical for the inhibition of the invasion and metastasis. Thus TBP-2, as a novel regulatory molecule of TGF-? signaling, is likely to be a prognostic indicator or a potential therapeutic target for preventing tumor progression.

SUBMITTER: Masaki S

PROVIDER: S-EPMC3387201 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Deficiency of thioredoxin binding protein-2 (TBP-2) enhances TGF-β signaling and promotes epithelial to mesenchymal transition.

Masaki So S Masutani Hiroshi H Yoshihara Eiji E Yodoi Junji J

PloS one 20120629 6

<h4>Background</h4>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 unclea ...[more]

PMID: 22768160

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