BRD4 inhibitor inhibits colorectal cancer growth and metastasis.
BRD4 inhibitor inhibits colorectal cancer growth and metastasis.
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DOI：
10.3390/ijms16011928
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发表时间：
2015-01-16
影响因子：
5.6
通讯作者：
Zhang DY
中科院分区：
文献类型：
--
作者：
Hu Y;Zhou J;Ye F;Xiong H;Peng L;Zheng Z;Xu F;Cui M;Wei C;Wang X;Wang Z;Zhu H;Lee P;Zhou M;Jiang B;Zhang DY
翻译后修饰在癌症中非常重要，赖氨酸乙酰化可以吸引多功能转录因子BRD4，已被确定为潜在的治疗靶点。在本文中，我们发现BRD4在结直肠癌中具有重要作用；它的抑制作用基本上消灭了肿瘤细胞。用抑制剂MS417治疗可以有效地影响癌细胞，尽管这种影响并不总是完全坏死或凋亡。我们报道，BRD4抑制还通过调节上皮-间质转化（EMT）过程中的几个关键蛋白来限制远端转移。BRD4抑制剂的这种作用已通过动物模型肝转移以及体外迁移和侵袭实验得到证实。总之，我们的研究结果证明了BRD4抑制剂的新应用，由于其限制转移的能力，同时也具有杀瘤作用，可能具有临床应用价值。
Post-translational modifications have been identified to be of great importance in cancers and lysine acetylation, which can attract the multifunctional transcription factor BRD4, has been identified as a potential therapeutic target. In this paper, we identify that BRD4 has an important role in colorectal cancer; and that its inhibition substantially wipes out tumor cells. Treatment with inhibitor MS417 potently affects cancer cells, although such effects were not always outright necrosis or apoptosis. We report that BRD4 inhibition also limits distal metastasis by regulating several key proteins in the progression of epithelial-to-mesenchymal transition (EMT). This effect of BRD4 inhibitor is demonstrated via liver metastasis in animal model as well as migration and invasion experiments in vitro. Together, our results demonstrate a new application of BRD4 inhibitor that may be of clinical use by virtue of its ability to limit metastasis while also being tumorcidal.
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