A new editorial paper was published in Oncotarget titled “Unveiling the non-canonical functions of EZH2 in prostate cancer.”

Prostate cancer (PCa) is ranked as the second leading cause of cancer-related death among American men excluding skin cancer. In this new editorial, researchers Yang Yi, Yanqiang Li, Kaifu Chen, and Qi Cao from Northwestern University’s Feinberg School of Medicine discuss a well-known oncogenic driver in PCa: enhancer of zeste homolog 2 (EZH2)—canonically known for the functions as the catalytic subunit of Polycomb Repressive Complex 2 (PRC2) that deposes histone H3 lysine 27 mono, di-, and tri-methylation (H3K27me1-3) and represses transcription.

“Although the oncogenic role of EZH2 mainly relies on its enzymatic activity and the PRC2, accumulating evidence suggests that targeting the lysine methyltransferase activity of EZH2 alone is ineffective in treating EZH2-dependent malignancies including PCa,” say the researchers.

Hence, deeply investigating the multifaceted tumorigenic functions of EZH2 will shed new light on understanding the etiology of PCa. It is noteworthy that two recent studies published in Nature Cell Biology and Oncogene by Yi et al. described previously unrecognized roles of EZH2 in regulation of translation and coactivation of transcription, respectively. In both cases, EZH2 exerts oncogenic functions independently of PRC2 and H3K27me3 to promote tumorigenesis and aggressiveness in PCa.

“In summary, both articles by Yi et al. emphasized the significance of non-canonical functions of EZH2 during PCa development, which may provide novel insights into the advancement of EZH2-targeting strategies to treat PCa patients. In fact, a new wave has been ushed for the discovery of EZH2 inhibitors to eliminate both the catalytic and non-catalytic activities of EZH2. Will these newly developed EZH2 degraders be successfully applied in PCa therapy? Will additional noncanonical functions of EZH2 be characterized in the PCa model? Let’s eagerly wait and see,” note the researchers.

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