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Fig. 7 | Molecular Cancer

Fig. 7

From: Targeting histone methyltransferase G9a inhibits growth and Wnt signaling pathway by epigenetically regulating HP1α and APC2 gene expression in non-small cell lung cancer

Fig. 7

Hypothetic schematic model of the underlying mechanisms of targeting G9a to suppress NSCLC. a Gene amplification [14], hypoxia [51], and/or other unknown mechanisms lead G9a overexpressed in cancers. G9a dimethylates H3K9, creating a binding site for HP1 (α, β, or γ, a structural chromosomal protein involved in transcription, chromatin organization, and replication as well as DNA repair), HP1 stabilizes and enhances the DNA methyltransferase activity of DNMT1. G9a also interacts with DNMT1, and then through this interaction G9a epigenetically regulates gene expression. In lung cancer, upregulated G9a may silence gene expression of these critical inhibitors of Wnt signaling pathway such as APC2, WIF1, and other tumor suppressors through DNA hypermethylation, resulting in overactivation of Wnt signaling pathway and enhanced growth. b Targeting G9a by the specific inhibitor UNC0638 down-regulates HP1α, and epigenetically restores expression of APC2 and other tumor suppressors through promoter demethylation, and then significantly inhibits Wnt signaling pathways and growth of NSCLC

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Molecular Cancer

ISSN: 1476-4598