| Literature DB >> 26659825 |
Han Xu1,2, Kexin Xu1,2,3, Housheng H He1,2,3, Chongzhi Zang1,2, Chen-Hao Chen1,2, Yiwen Chen1,2, Qian Qin2, Su Wang2, Chenfei Wang2, Shengen Hu2, Fugen Li2, Henry Long2, Myles Brown2,3, X Shirley Liu1,2,4.
Abstract
UNLABELLED: Overexpression of EZH2 is frequently linked to the advanced and metastatic stage of cancers. The mechanisms of its oncogenic function can be context specific, and may vary depending on the protein complexes that EZH2 interacts with. To identify novel transcriptional collaborators of EZH2 in cancers, a computational approach was developed that integrates protein-DNA binding data, cell perturbation gene expression data, and compendiums of tumor expression profiles. This holistic approach identified E2F1, a known mediator of the Rb tumor suppressor, as a transcriptional collaborator of EZH2 in castration-resistant prostate cancer. Subsequent analysis and experimental validation found EZH2 and E2F1 cobind to a subset of chromatin sites lacking H3K27 trimethylation, and activate genes that are critical for prostate cancer progression. The collaboration of EZH2 and E2F1 in transcriptional regulation is also observed in diffuse large B-cell lymphoma cell lines, where activation of the transcriptional network is concordant with the cellular response to the EZH2 inhibitor. IMPLICATIONS: The direct collaboration between EZH2 and Rb/E2F1 pathway provides an innovative mechanism underlying the cascade of tumor progression, and lays the foundation for the development of new anticancer targets/strategies. ©2015 American Association for Cancer Research.Entities:
Mesh：
Substances：
Year: 2015 PMID： 26659825 PMCID： PMC4828727 DOI： 10.1158/1541-7786.MCR-15-0313
Source DB: PubMed Journal: Mol Cancer Res ISSN： 1541-7786 Impact factor: 5.852