EZH2 is a promising anticancer drug target. However, factors that determine its oncogenic function are still obscure. In this study, Xu and colleagues use a computational integrative approach to infer critical components in EZH2-involved transcriptional signaling. E2F1 was identified as a transcriptional collaborator of EZH2 in castration resistant prostate cancer. These two tumor-driving proteins co-localize at chromatin sites lacking H3K27 trimethylation, and activate genes that promote prostate cancer progression. The collaboration of EZH2 and E2F1 is also involved in the regulation of gene expression upon EZH2 inhibitor treatment in lymphoma cells. This work lays the foundation for novel anticancer targets and strategies.

Diep and coworkers performed gene expression profiling and biochemical studies in PR-A or PR-B containing ovarian cancer models. PR-A represses, while PR-B induces FOXO1 and p21, required mediators of ovarian cancer cellular senescence. FOXO1 add-back to PR-A-only expressing cells induced PR-A phosphorylation at Ser294, conferred PR-B-like activity to...

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