Chien Yi-Chung, Liu Liang-Chih, Ye Han-Yu, Wu Jia-Yan, Yu Yung-Luen
Graduate Institute of Biomedical Sciences, China Medical UniversityTaichung 40454, Taiwan.
Center for Molecular Medicine, China Medical University HospitalTaichung 404, Taiwan.
Am J Cancer Res. 2018 Mar 1;8(3):422-434. eCollection 2018.
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 transcription, leading to increased activity of MMP-2 and MMP-9 and thus to increased invasive activity of TNBC cells.
三阴性乳腺癌（TNBC）比其他类型的乳腺癌具有更高的侵袭和转移潜能。zeste同源物2增强子（EZH2）是多梳抑制复合物2（PRC2）中的催化核心蛋白，它催化组蛋白H3赖氨酸27位点的三甲基化（H3K27me3），并介导参与基本细胞过程（如细胞命运决定、细胞周期调控、衰老、细胞分化和癌症形成）的靶基因的基因沉默。TNBC转移与EZH2之间的一致关联尚未得到证实。本研究的目的是探讨EZH2在调节金属蛋白酶组织抑制剂（TIMPs）和基质金属蛋白酶（MMPs）以促进TNBC细胞转移中的作用，并鉴定TNBC细胞中受EZH2调节的转移相关基因。我们发现，高水平的EZH2表达会诱导转录抑制，导致MMP-2和MMP-9活性增加，从而导致TNBC细胞侵袭活性增加。
