Macrophages-stimulated PRMT1-mediated EZH2 methylation promotes breast cancer 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. •PRMT1 is required for TAMs-mediated breast cancer metastasis.•TAMs stimulate PRMT1 expression by secreting IL-6.•TAMs promote breast cancer metastasis through IL-6-PRMT1-CDK1-TRAF6-EZH2 axis.•CD163 (a TAMs marker) is positive correlated with PRMT1, meR342-EZH2 and EZH2 expression in breast cancer samples.