BRD4 Inhibitor Inhibits Colorectal Cancer Growth and Metastasis

被引：82

作者：

Hu, Yuan ^{[1
,2
]}

Zhou, Jieqiong ^{[1
]}

Ye, Fei ^{[2
]}

Xiong, Huabao ^{[3
]}

Peng, Liang ^{[3
]}

Zheng, Zihan ^{[4
]}

Xu, Feihong ^{[3
]}

Cui, Miao ^{[2
]}

Wei, Chengguo ^{[5
]}

Wang, Xinying ^{[1
]}

Wang, Zhongqiu ^{[1
]}

Zhu, Hongfa ^{[2
]}

Lee, Peng ^{[6
]}

Zhou, Mingming ^{[7
]}

Jiang, Bo ^{[1
]}

Zhang, David Y. ^{[2
]}

机构：

[1] Southern Med Univ, Nanfang Hosp, Dept Gastroenterol, Guangdong Prov Key Lab Gastroenterol, Guangzhou 510515, Guangdong, Peoples R China

[2] Icahn Sch Med Mt Sinai, Dept Pathol, New York, NY 10029 USA

[3] Icahn Sch Med Mt Sinai, Dept Med, Inst Immunol, New York, NY 10029 USA

[4] Univ N Carolina, Coll Arts & Sci, Chapel Hill, NC 27514 USA

[5] Icahn Sch Med Mt Sinai, Dept Med Bioinformat Core, New York, NY 10029 USA

[6] NYU, Dept Pathol, NYU Canc Inst, New York Harbor Healthcare Syst,Sch Med, New York, NY 10010 USA

[7] Icahn Sch Med Mt Sinai, Dept Struct & Chem Biol, New York, NY 10029 USA

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2015年 / 16卷 / 01期

关键词：

colorectal cancer; BRD4; MS417; metastasis; epithelial-to-mesenchymal transition (EMT); GENE-EXPRESSION; BREAST-CANCER; BET BROMODOMAINS; KIDNEY-DISEASE; CHROMATIN; TRANSCRIPTION; CELLS; CARCINOMA; LEUKEMIA; PROLIFERATION;

D O I：

10.3390/ijms16011928

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1928 / 1948

页数：21

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