Macrophages-stimulated PRMT1-mediated EZH2 methylation promotes breast cancer metastasis

Zhongwei Li; Diandian Wang; Wenwen Wang; Xintian Chen; Anqun Tang; Pingfu Hou; Minle Li; Junnian Zheng; Jin Bai

doi:10.1016/j.bbrc.2020.10.037

Macrophages-stimulated PRMT1-mediated EZH2 methylation promotes breast cancer metastasis

Biochem Biophys Res Commun. 2020 Dec 17;533(4):679-684. doi: 10.1016/j.bbrc.2020.10.037. Epub 2020 Oct 20.

Authors

Zhongwei Li¹, Diandian Wang², Wenwen Wang², Xintian Chen², Anqun Tang¹, Pingfu Hou¹, Minle Li¹, Junnian Zheng³, Jin Bai⁴

Affiliations

¹ Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
² Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
³ Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. Electronic address: jnzheng@xzhmu.edu.cn.
⁴ Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. Electronic address: bj@xzhmu.edu.cn.

PMID: 33092789
DOI: 10.1016/j.bbrc.2020.10.037

Abstract

Tumor-associated macrophages (TAMs) are important monocytes in the breast cancer microenvironment. They facilitate the distant metastasis of breast cancer. However, the detailed mechanisms of TAM-derived cancer metastasis have not been clearly elucidated. Here, we demonstrate that PRMT1 is essential for TAM-mediated breast cancer cell migration and metastasis. TAMs increase EZH2 stability by stimulating PRMT1-mediated meR342-EZH2 formation through the secretion of interleukin-6 (IL-6) cytokine. Moreover, high expression levels of TAMs are positively correlated with PRMT1, meR342-EZH2, and EZH2 expression in breast cancer patients. Our study presents a novel mechanism of TAM-induced breast cancer metastasis via the IL-6-PRMT1-meR342-EZH2 axis.

Keywords: Cancer metastasis; EZH2; IL-6; PRMT1; Post-translational modifications; Tumor-associated macrophages.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Breast Neoplasms / metabolism*
Breast Neoplasms / pathology
Cell Line, Tumor
Cell Movement / genetics
Enhancer of Zeste Homolog 2 Protein / metabolism*
Female
Gene Expression Regulation, Neoplastic / genetics
Humans
Immunohistochemistry
Interleukin-6 / metabolism
Intracellular Signaling Peptides and Proteins / metabolism
Macrophages / metabolism*
Methylation
Mice
Mice, Inbred BALB C
Neoplasm Metastasis
Protein Stability
Protein-Arginine N-Methyltransferases / genetics
Protein-Arginine N-Methyltransferases / metabolism*
Repressor Proteins / genetics
Repressor Proteins / metabolism*
Tumor Microenvironment / genetics
Ubiquitination
Xenograft Model Antitumor Assays

Substances

Interleukin-6
Intracellular Signaling Peptides and Proteins
Repressor Proteins
Tifab protein, human
PRMT1 protein, human
Protein-Arginine N-Methyltransferases
EZH2 protein, human
Enhancer of Zeste Homolog 2 Protein