American Association for Cancer Research
15417786mcr130546-sup-mcr-13-0542figlegsfigs1-4.pdf (432.31 kB)

Supplementary Figure Legends, Figures 1 - 4 from EZH2: Not EZHY (Easy) to Deal

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journal contribution
posted on 2023-04-03, 16:26 authored by Gauri Deb, Anup Kumar Singh, Sanjay Gupta

PDF file - 433KB, S1: CIP2A and SET levels are increased in some primary human pancreatic cancer samples. S2: Increased expression of PP2A inhibitors trend toward decreased PP2A activity, which trends toward increased Myc expression and Myc protein stabilization in pancreatic cancer cell lines. S3: OP449 treatment decreases c-Myc DNA binding and half-life in pancreatic cancer cell lines, and SET knockdown reduces OP449 sensitivity. S4: OP449 treatment reduces pancreatic cancer cell migration in vitro, proliferation in vivo, and increases tumor cell apoptosis in vivo.



Seminal discoveries have established that epigenetic modifications are important for driving tumor progression. Polycomb group (PcG) proteins are highly conserved epigenetic effectors that maintain, by posttranslational modification of histones, the silenced state of genes involved in critical biologic processes, including cellular development, stem cell plasticity, and tumor progression. PcG proteins are found in two multimeric protein complexes called Polycomb repressive complexes: PRC1 and PRC2. Enhancer of zeste homolog 2 (EZH2), catalytic core subunit of PRC2, epigenetically silences several tumor-suppressor genes by catalyzing the trimethylation of histone H3 at lysine 27, which serves as a docking site for DNA methyltransferases and histone deacetylases. Evidence suggests that overexpression of EZH2 is strongly associated with cancer progression and poor outcome in disparate cancers, including hematologic and epithelial malignancies. The regulatory circuit and molecular cues causing EZH2 deregulation vary in different cancer types. Therefore, this review provides a comprehensive overview on the oncogenic role of EZH2 during tumorigenesis and highlights the multifaceted role of EZH2, as either a transcriptional activator or repressor depending on the cellular context. Additional insight is provided on the recent understanding of the causes and consequences of EZH2 overexpression in specific cancer types. Finally, evidence is discussed on how EZH2 has emerged as a promising target in anticancer therapy and the prospects for targeting EZH2 without affecting global methylation status. Thus, a better understanding of the complex epigenetic regulatory network controlling EZH2 expression and target genes facilitates the design of novel therapeutic interventions. Mol Cancer Res; 12(5); 639–53. ©2014 AACR.

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