據(jù)英國(guó)《獨(dú)立報(bào)》8月22日?qǐng)?bào)道,，英國(guó)科學(xué)家在細(xì)菌體內(nèi)發(fā)現(xiàn)了一種能阻止乳腺癌惡化的分子，有助于科學(xué)家們?cè)O(shè)計(jì)出療效更強(qiáng)的抗乳腺癌藥物,。研究發(fā)表在最新一期《自然—化學(xué)》雜志上。
這種硫鏈絲菌肽分子會(huì)抑制出現(xiàn)在很多乳腺癌細(xì)胞中的一種致癌蛋白質(zhì)FOXM1,。FOXM1會(huì)開啟調(diào)控細(xì)胞生長(zhǎng)和分裂的基因,，導(dǎo)致腫瘤擴(kuò)散并觸發(fā)血管的生長(zhǎng)?？茖W(xué)家們表示,，阻止這種蛋白質(zhì)能在癌癥處于早期時(shí)預(yù)防其進(jìn)一步惡化，同時(shí)阻止癌細(xì)胞的生長(zhǎng)和擴(kuò)散,。
英國(guó)癌癥研究所的香卡·巴拉蘇伯蘭馬尼安教授表示：“此前,，我們從來(lái)沒有意識(shí)到有天然物質(zhì)能直接攻擊控制基因活動(dòng)的蛋白質(zhì)，然而,，令人驚奇的是,，我們發(fā)現(xiàn)，細(xì)菌中有個(gè)分子在攻擊控制基因活動(dòng)的蛋白質(zhì)方面表現(xiàn)良好,，其能關(guān)閉乳腺癌細(xì)胞中的致癌基因,，而且這種分子也有強(qiáng)烈的抗生素效應(yīng)。”
英國(guó)癌癥研究所癌癥信息中心主管萊斯利·沃爾克表示：“發(fā)現(xiàn)這個(gè)簡(jiǎn)單的細(xì)菌如何擁有這么強(qiáng)大的能力是我們對(duì)抗乳腺癌惡化和擴(kuò)散的關(guān)鍵,。”(生物谷 Bioon.com)
doi:10.1038/nchem.1114
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The transcription factor FOXM1 is a cellular target of the natural product thiostrepton
Nagaratna S. Hegde; Deborah A. Sanders; Rapha?l Rodriguez; Shankar Balasubramanian
Transcription factors are proteins that bind specifically to defined DNA sequences to promote gene expression. Targeting transcription factors with small molecules to modulate the expression of certain genes has been notoriously difficult to achieve. The natural product thiostrepton is known to reduce the transcriptional activity of FOXM1, a transcription factor involved in tumorigenesis and cancer progression. Herein we demonstrate that thiostrepton interacts directly with FOXM1 protein in the human breast cancer cells MCF-7. Biophysical analyses of the thiostrepton–FOXM1 interaction provide additional insights on the molecular mode of action of thiostrepton. In cellular experiments, we show that thiostrepton can inhibit the binding of FOXM1 to genomic target sites. These findings illustrate the potential druggability of transcription factors and provide a molecular basis for targeting the FOXM1 family with small molecules.
