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

American Journal of Cancer Research

Liang-Chih Liu¹  Yung-Luen Yu²  Han-Yu Ye³  Yi-Chung Chien⁴  Jia-Yan Wu⁵ 

[1] Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan;Department of Biotechnology, Asia University, Taichung 413, Taiwan;Department of Surgery, China Medical University Hospital, Taichung 404, Taiwan;Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40454, Taiwan;School of Medicine, College of Medicine, China Medical University, Taichung 404, Taiwan

关键词: Enhancer of zeste homolog 2;    matrix metalloproteinases;    tissue inhibitor of metalloproteinase;    migration;    triple-negative breast cancer cell;   

DOI  :  

学科分类：肿瘤学

来源: e-Century Publishing Corporation

【 摘 要 】

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.

【 授权许可】

CC BY-NC