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

• DOI: 10.1016/j.bbrc.2020.10.037
• Publication Date: 2020-10-20T07:36:24Z
• Authors: Zhongwei Li; Diandian Wang; Wenwen Wang; Xintian Chen; Anqun Tang; Pingfu Hou; Minle Li; Junnian Zheng; Jin Bai
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; Protein-Arginine N-Methyltransferases; Interleukin-6; Protein Stability; Macrophages; Intracellular Signaling Peptides and Proteins; Breast Neoplasms; Immunohistochemistry; Methylation; 3. Good health; Gene Expression Regulation, Neoplastic; Repressor Proteins; Mice; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Tumor Microenvironment; Animals; Humans; Enhancer of Zeste Homolog 2 Protein; Female; Neoplasm Metastasis

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.