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Regulation of CCL2 by EZH2 affects tumor-associated macrophages polarization and infiltration in breast cancer

文献类型：期刊论文

作者Wang, Ya-fang3,4; Yu, Lei2,4; Hu, Zong-long4; Fang, Yan-fen4; Shen, Yan-yan4; Song, Min-fang1; Chen, Yi2,4
刊名CELL DEATH & DISEASE
出版日期2022-08-29
卷号13期号:8页码:15
ISSN号2041-4889
DOI10.1038/s41419-022-05169-x
通讯作者Wang, Ya-fang(wangyf2@shanghaitech.edu.cn) ; Chen, Yi(ychen@simm.ac.cn)
英文摘要Tumor associated macrophages (TAMs) play an important role in tumorigenesis, development and anti-cancer drug therapy. However, very few epigenetic compounds have been elucidated to affect tumor growth by educating TAMs in the tumor microenvironment (TME). Herein, we identified that EZH2 performs a crucial role in the regulation of TAMs infiltration and protumoral polarization by interacting with human breast cancer (BC) cells. We showed that EZH2 inhibitors-treated BC cells induced M2 macrophage polarization in vitro and in vivo, while EZH2 knockdown exhibited the opposite effect. Mechanistically, inhibition of EZH2 histone methyltransferase alone by EZH2 inhibitors in breast cancer cells could reduce the enrichment of H3K27me3 on CCL2 gene promoter, elevate CCL2 transcription and secretion, contributing to the induction of M2 macrophage polarization and recruitment in TME, which reveal a potential explanation behind the frustrating results of EZH2 inhibitors against breast cancer. On the contrary, EZH2 depletion led to DNA demethylation and subsequent upregulation of miR-124-3p level, which inhibited its target CCL2 expression in the tumor cells, causing arrest of TAMs M2 polarization. Taken together, these data suggested that EZH2 can exert opposite regulatory effects on TAMs polarization through its enzymatic or non-enzymatic activities. Our results also imply that the effect of antitumor drugs on TAMs may affect its therapeutic efficacy, and the combined application with TAMs modifiers should be warranted to achieve great clinical success.
WOS关键词METHYLATION ; CHEMOKINES ; SILENCES ; CELL
资助项目National Natural Sciences foundation of China[81803557] ; Lingang Laboratory[LG202103-02-05]
WOS研究方向Cell Biology
语种英语
出版者SPRINGERNATURE
WOS记录号WOS:000847374000002
源URL[http://119.78.100.183/handle/2S10ELR8/302420]  
专题中国科学院上海药物研究所
通讯作者Wang, Ya-fang; Chen, Yi
作者单位1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Ya-fang,Yu, Lei,Hu, Zong-long,et al. Regulation of CCL2 by EZH2 affects tumor-associated macrophages polarization and infiltration in breast cancer[J]. CELL DEATH & DISEASE,2022,13(8):15.
APA Wang, Ya-fang.,Yu, Lei.,Hu, Zong-long.,Fang, Yan-fen.,Shen, Yan-yan.,...&Chen, Yi.(2022).Regulation of CCL2 by EZH2 affects tumor-associated macrophages polarization and infiltration in breast cancer.CELL DEATH & DISEASE,13(8),15.
MLA Wang, Ya-fang,et al."Regulation of CCL2 by EZH2 affects tumor-associated macrophages polarization and infiltration in breast cancer".CELL DEATH & DISEASE 13.8(2022):15.

入库方式： OAI收割

来源：上海药物研究所

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