硫链丝菌肽分子能阻止乳腺癌恶化

据英国《独立报》8月22日报道，英国科学家在细菌体内发现了一种能阻止乳腺癌恶化的分子，有助于科学家们设计出疗效更强的抗乳腺癌药物。研究发表在最新一期《自然—化学》杂志上。

这种硫链丝菌肽分子会抑制出现在很多乳腺癌细胞中的一种致癌蛋白质FOXM1。FOXM1会开启调控细胞生长和分裂的基因，导致肿瘤扩散并触发血管的生长。科学家们表示，阻止这种蛋白质能在癌症处于早期时预防其进一步恶化，同时阻止癌细胞的生长和扩散。

英国癌症研究所的香卡·巴拉苏伯兰马尼安教授表示：“此前，我们从来没有意识到有天然物质能直接攻击控制基因活动的蛋白质，然而，令人惊奇的是，我们发现，细菌中有个分子在攻击控制基因活动的蛋白质方面表现良好，其能关闭乳腺癌细胞中的致癌基因，而且这种分子也有强烈的抗生素效应。”

英国癌症研究所癌症信息中心主管莱斯利·沃尔克表示：“发现这个简单的细菌如何拥有这么强大的能力是我们对抗乳腺癌恶化和扩散的关键。”(生物谷 Bioon.com)

doi:10.1038/nchem.1114

PMC:
PMID:

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.