轉(zhuǎn)化生長因子β（TGF-β）具有調(diào)節(jié)細(xì)胞生長、分化,、凋亡,、侵襲和各種癌癥細(xì)胞的上皮間質(zhì)轉(zhuǎn)化（EMT）等關(guān)鍵作用。TGF-β誘導(dǎo)的EMT是癌細(xì)胞侵襲的重要一步,。
硫氧還蛋白結(jié)合蛋白2 （TBP-2）在多種癌癥類型中都表達下調(diào),，其表達不足的結(jié)果就是促發(fā)癌癥患者的早期發(fā)病。不過,，目前還不清楚TBP-2如何抑制癌癥的侵襲和轉(zhuǎn)移,。PLoS ONE雜志上的一項研究中，科學(xué)家證明TBP-2的缺乏增加TGF-β的轉(zhuǎn)錄活性,，也增強了TGF-β誘導(dǎo)Smad2磷酸化水平的功效,。
敲除TBP-2能增強TGF-β調(diào)控Snail和Slug的表達，Snail和Slug是介導(dǎo)TGF-β誘導(dǎo)的EMT關(guān)鍵轉(zhuǎn)錄因子,，TBP-2表達的降低能促進TGF-β誘導(dǎo)的A549細(xì)胞紡錘狀形態(tài)的形成以及降低E-鈣粘素的表達,。
研究結(jié)果表明TBP-2缺失增強TGF-β的信號，促進TGF-β誘導(dǎo)的EMT,。抑制TGF-β誘導(dǎo)的EMT對于侵襲和轉(zhuǎn)移的抑制是至關(guān)重要的,。因此，TBP-2是受TGF-β信號調(diào)控的一種新型分子,，很可能是一個腫瘤預(yù)后指標(biāo),，是腫瘤治療的潛在靶標(biāo)。（生物谷：Bioon.com）
doi:10.1371/journal.pone.0039900
PMC:
PMID:
Deficiency of Thioredoxin Binding Protein-2 (TBP-2) Enhances TGF-β Signaling and Promotes Epithelial to Mesenchymal Transition
So Masaki1, Hiroshi Masutani1, Eiji Yoshihara1, Junji Yodoi1,2*
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.
Principal Findings
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/Significance
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.
