BRD4 inhibitor inhibits colorectal cancer growth and metastasis

Yuan Hu, Jieqiong Zhou, Fei Ye, Huabao Xiong, Liang Peng, Zihan Zheng, Feihong Xu, Miao Cui, Chengguo Wei, Xinying Wang, Zhongqiu Wang, Hongfa Zhu, Peng Lee, Mingming Zhou, Bo Jiang, David Y. Zhang

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1928-1948
Number of pages21
JournalInternational Journal of Molecular Sciences
Volume16
Issue number1
DOIs
StatePublished - 16 Jan 2015

Keywords

  • BRD4
  • Colorectal cancer
  • Epithelial-to-mesenchymal transition (EMT)
  • MS417
  • Metastasis

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