EZH2 AND FOXM1 CROSSTALK IN TRIPLE NEGATIVE BREAST CANCER

Abstract

Both EZH2 and FOXM1 have been consistently shown to be upregulated in aggressive breast cancer and in this study, we sought to dissect the crosstalk between EZH2 and FOXM1 in TNBC. By combining microarray data in TNBC cell line with TCGA patient database, we observed a positive correlation between EZH2 and FOXM1. Subsequent in-vitro cell-based assays showed that EZH2 positively modulated FOXM1-mediated invasion pathway with co-occupancy of EZH2 and FOXM1 on the promoter of MMP2 and MMP7. Interestingly, the canonical function of EZH2 was not completely loss. In accordance to this, we also identified occupancy of PRC2 complex and its associated repressive H3K27me3 mark on the same MMPs promoters. Taken together, this study proposed a model highlighting dual regulation of EZH2 in regulating MMP-mediated invasion in TNBC subtype. The balance between canonical and non-canonical roles of EZH2 could possibly be the determining factor in promoting a more aggressive breast cancer.