Epigenetic regulation of signaling pathways in cancer: role of the histone methyltransferase EZH2.

EZH2 is the histone H3 lysine 27 methyltransferase of polycomb-repressive complex 2. It transcriptionally silences cohorts of developmental regulators in stem/progenitors and cancer cells. EZH2 is essential in maintaining stem cell identity by globally repressing differentiation programs. Analogously, it plays a key role in oncogenesis by targeting signaling molecules that control cell differentiation. Emerging data indicate that EZH2 promotes cancer formation and progression through epigenetic activation of oncogenic signaling cascades and inhibition of pro-differentiation pathways. Genome-wide mapping analysis has been expanding the repertoire of target genes and the associated signaling pathways regulated by EZH2. Better understanding of the molecular basis of such regulations in various cancer types will help establish EZH2-mediated epigenetic silencing as a therapeutic target.