Table 1. Some metastasis associated target genes epigenetically repressed by EZH2 in breast and prostate cancer.

Cancer type	EZH2 target genes	Possible functional role in metastasis	Mechanism	Model system	Reference
Breast cancer	FOXC1	Increased in vitro and in vivo migration and metastasis	Enhanced H3K27me3 and reduced H3 and H4 acetylation at the promoter	MCF-7 MDA-MB-231	Juan et al.;2012 Breast Cancer Research
	RAD51paralogs RAD51B/RAD51L1 RAD51C/RAD51L2 RAD51D/RAD51L3 XRCC2 XRCC3	Unrepaired chromosome breaks, aneuploidy, Defective homologous recombination (HR) Impaired DNA repair	Not proposed	MCF10A MCF-7 SUM102	Ziedlier et al.;2005 Neoplasia
	CDKN1C (p57KIP2)	Aberrant cell proliferation and tumor growth	Increased H3K27me3 Reduced H3K9/14 acetylation and H3K4me3 at the promoter	SK-BR-3 BT-474 MDA-MB-231 MCF10A	Yang et al.;2005 Plos one
	*RUNX3	Increased cell proliferation	H3K27me3 and HDAC1 mediated repression	MCF-7 LNCaP	Fujii et al. ;2008,JBC
	*RKIP	Accelerates cell invasion and metastasis	H3K27me3 and H3K9me3 mediated repression and involvement of Snail in the recruitment of EZH2 repressive complex	T47D MCF-7 MDAMB231 DU145 PC3 LNCaP	Gang Ren et al.;2012–12–10 Cancer Research
Prostate Cancer	CIITA	Decreased expression of cell surface MHC II which enables tumor cells to escape immune system	Enhanced H3K27me3 repressive mark at the promoter	MDA-MB-435 variants	Agnieszka D Truax et al.; Plos one 2012
	Kruppel like Factor 2	Suppression of cell growth and anti-angiogenesis	Increase in H3K27me3 and depletion of phosphorylated serine 2 of RNA polymerase at the promoter	MDA-MB-231 MCF-7	Taniguchi et al. ;2012, Oncogene
	NF-κB targets such as IL6, TNF, BIRC3 and IL8	Inflammation, oncogenesis and tumor dissemination	Histone methyltransferase independent function in ER negative breast cancer cells ; Binding of ternary complex containing EZH2, RelA and RelB to target promoters positively modulate their expression and released cytokines induces a positive feedback loop resulting in constitutive expression of NF-κB	MDA-MB-231	Lee et al.; 2011;Cell
	IL6, IL8		In ER positive cells PRC2 complex is recruited by ER and EZH2 functions as an epigenetic repressor of target genes by catalyzing H3K27me3	MCF-7 T47D
	DAB2IP	Loss of expression promotes epithelial to mesenchymal transition (EMT).	Recruitment of PRC2 complex to the hDAB2IP promoter region accompanied with the increased levels of methyl histone H3 (H3) and histone deacetylase (HDAC1)	LNCaP C4–2 PC3	Chen et al.;2005;JBC Xie et al.;2009;PNAS
	MSMB (encodes PSP94)	Loss of function may cause inhibition of tumor cell apoptosis, decrease tumor associated, vascular endothelial growth factor (VEGF)-mediated vascularization and enhance secretion of matrix Metalloproteinases involved in metastasis	EZH2 associates with MSMB gene promoter and catalyzes H3K27 trimethylation. Additionally, hypoacetylation of histone H3K9 and the hypermethylation of a CpG island in the target promoter also contribute to the gene silencing.	LNCaP PC3 DU145	Beke et al.;2007;Oncogene
	SLIT2	Repression may cause enhanced prostate cancer cell proliferation and invasion	EZH2 mediated H3K27 trimethylation .Also, CpG islands in SLIT2 promoter were also reported to be hypermethylated in prostate cancer cells.	LNCaP DU145 PC3	Yu et al.;2010;Oncogene
	*E-Cadherin	Loss of expression confers invasive phenotype and promotes EMT.	H3K27me3 mediated repression by EZH2 and other PRC2 members localized at the target gene promoter.	DU145 H16N2	Cao et al.;2008;Oncogene
	ADRB2	Inhibition confers invasive phenotype and increased motility to benign prostate cancer cells.	Strong enrichment of ADRB2 promoter by EZH2, SUZ12 and H3K27me3 indicates EZH2 mediated transcriptional repression.	LNCaP DU145	Yu et al. ; 2007 ; Cell
	TIMP-2 and TIMP-3	Repression causes enhanced invasion and metastasis by increased MMP-9 activity.	EZH2 mediated H3K27 methylation and subsequent promoter DNA methylation	LNCaP PC3 DU145	Shin et al.; 2012 ; Plos one

^* Silenced in both breast and prostate cancers