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.
Copyright © 2020 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology
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Cell Line, Tumor
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Cell Movement / genetics
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Enhancer of Zeste Homolog 2 Protein / metabolism*
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Female
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Gene Expression Regulation, Neoplastic / genetics
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Humans
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Immunohistochemistry
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Interleukin-6 / metabolism
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Intracellular Signaling Peptides and Proteins / metabolism
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Macrophages / metabolism*
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Methylation
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Mice
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Mice, Inbred BALB C
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Neoplasm Metastasis
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Protein Stability
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Protein-Arginine N-Methyltransferases / genetics
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Protein-Arginine N-Methyltransferases / metabolism*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Tumor Microenvironment / genetics
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Ubiquitination
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Xenograft Model Antitumor Assays
Substances
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Interleukin-6
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Intracellular Signaling Peptides and Proteins
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Repressor Proteins
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Tifab protein, human
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PRMT1 protein, human
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Protein-Arginine N-Methyltransferases
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EZH2 protein, human
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Enhancer of Zeste Homolog 2 Protein