EZH2 promotes migration and invasion of triple-negative breast cancer cells via regulating TIMP2-MMP-2/-9 pathway

Abstract

Triple-negative breast cancer (TNBC) has a higher potential for invasion and metastasis than other types of breast cancer. Enhancer of zeste homolog 2 (EZH2) is the catalytic core protein in the polycomb repressive complex 2 (PRC2), which catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3) and mediates gene silencing of the target genes that are involved in fundamental cellular processes, such as the cell fate decision, cell cycle regulation, senescence, cell differentiation, and cancer formation. A consistent association between TNBC metastasis and EZH2 has not been confirmed. The aim of this study was to investigate the role of EZH2 in the regulation of tissue inhibitor of metalloproteinase (TIMPs) and matrix metalloproteinases (MMPs) to promote metastasis of TNBC cells and to characterize the metastasis-associated genes regulated by EZH2 in TNBC cells. We found that high levels of EZH2 expression induce repression of TIMP2 transcription, leading to increased activity of MMP-2 and MMP-9 and thus to increased invasive activity of TNBC cells.