Symphony of epigenetic and metabolic regulation—interaction between the histone methyltransferase EZH2 and metabolism of tumor

Table 1 Effects of metabolites on post-translational modification of EZH2 protein

Type	Modification enzyme	Site	Biological Functions	Metabolites	Metabolic pathways	Ref.
Phosphorylation	AMPK	T311	Disrupts EZH2 interaction with SUZ12, suppresses PRC2 HMTase activity and releases target genes (OLIG2, SOX17, GATA6), resulting in cell cycle arrest and cell differentiation	ATP	Glucose metabolism (glycolysis, etc.)	[78]
	AKT	S21	Suppresses EZH2 HMTase activity and releases target genes (HOXA9), promoting tumor progression	ATP	Energy metabolism	[79]
		S21	Inhbits EZH2 HMTase activity and releases target genes (IGF1, BCL2, HIF1A), leading to the MM cell drug resistance	ATP	Energy metabolism	[83]
		S21	Activates EZH2 as a coactivator for critical transcription factors including the androgen receptor, promoting tumor cells growth	ATP	Energy metabolism	[31]
		S21	Facilitates EZH2-mediated STAT3 methylation and enhances EZH2-STAT3 interaction and STAT3 activity, which accelerates GSC self-renewal and glioblastoma tumor process	ATP	Energy metabolism	[28]
Acetylation	PCAF	K348	Enhances EZH2 stability and function and the migration and invasion ability of lung cancer	Acetyl-CoA	Fatty acid β-oxidation, TCA cycle, pyruvate and acetate metabolism	[94]
O-GlcNAcylation	OGT	S75	Enhances EZH2 stability and function, contributing to tumorigenesis	UDP-GlcNAc	Glucose, amino acids, fatty acids and nucleotide metabolism	[98]
		S73, S76, S84, T313, S729	Enhance EZH2 stability and function, promoting cancer progression			[99]
		——	Promotes the migration and invasion of advanced colorectal cancer by enhancing EZH2 stability and activity			[100]

ISSN: 1868-7083