Phosphorylation of EZH2 activates STAT3 signaling via STAT3 methylation and promotes tumorigenicity of glioblastoma stem-like cells
By Eunhee Kim, Mi-Suk Kim, Dong-Hun Woo, Y. Shin, Jihye Shin, Nakho Chang, Young-Taek Oh, Hong‐Gyum Kim, Jingeun Rheey, I. Nakano and 5 more. Cancer Cell, 2013
777 citations recorded by the source corpus.
SUMMARY Glioblastoma multiforme (GBM) displays cellular hierarchies harboring a subpopulation of stem-like cells (GSCs). Enhancer of Zeste Homolog 2 (EZH2), the lysine methyl transferase of Polycomb repressive complex 2, mediates transcriptional repression of pro-differentiation genes in both normal and neoplastic stem cells. An oncogenic role of EZH2 as a transcriptional silencer is well established; however, additional functions of EZH2 are incompletely understood. Here we show that EZH2 binds to and methylates STAT3, leading to enhanced STAT3 activity by increased tyrosine phosphorylation of STAT3. The EZH2-STAT3 interaction preferentially occurs in GSCs relative to non-stem bulk tumor cells, and it requires a specific phosphorylation of EZH2. Inhibition of EZH2 reverses the silencing of Polycomb target genes and diminishes STAT3 activity, suggesting therapeutic strategies.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/389f4c99ac06ef305292b22bcddcedce5bdada34
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Citations in the corpus
- Reconstructing and reprogramming the tumor propagating potential of glioblastoma stem-like cells (2014, neutral): “…point to the importance of understanding the epigenetic identities and susceptibilities of such aggressive subpopulations (Binda et al., 2012; Day et al., 2013; Friedmann-Morvinski et al., 2012; Kim et al., 2013; Piccirillo et al., 2006; Singh et al., 2004; Son et al., 2009; Suva et al., 2013).”
- Cancer stem cells in glioblastoma (2015, background): “Similarly, the H3K27 methylase EZH2 has been shown to be important for CSC maintenance through its function as a regulator of both Polycomb-repressive domains and STAT3 signaling (Kim et al. 2013).”