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MED1 induces M2 polarization of tumor-associated macrophages to aggravate breast cancer

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Abstract

Background

Breast cancer is a common malignant tumor in female, and its 5-year survival rate remains low. The correlation between mediator subunit 1 (MED1) gene and macrophage phenotypic transformation may be a key factor affecting the therapeutic effect on cancer.

Objective

The present study intended to explore the role of MED1 in macrophage polarization and its further influence on the malignant behaviors of breast cancer.

Methods

Bioinformatics analysis was carried out to predict the expression pattern of MED1 in breast cancer. Flow cytometry was conducted to detect the effect of MED1 overexpression or silencing on macrophage polarization. ELISA was applied to analyze the effect of abnormal MED1 expression on cytokine secretion of macrophages. CCK-8, colony formation, Transwell and scratch healing assays were applied to investigate the effects of macrophage conditioned medium on the malignant behaviors of breast cancer cells.

Results

MED1 expression was prominently increased in M2 macrophages, and overexpression of MED1 significantly increased M2 polarization of tumor-associated macrophages (TAMs) and IL-10 cytokine level. Meanwhile, M2 macrophages with MED1 overexpression could significantly promote the malignant behaviors of breast cancer cells. Dasatinib rescue experiment further confirmed that MED1-induced M2 macrophage polarization could facilitate the malignant progression of breast cancer cells.

Conclusion

In summary, MED1 could induce M2 macrophage polarization and thus regulate the malignant behaviors of breast cancer cells.

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Funding

This study was supported by Shanghai Fengxian District Science and Technology Commission Social Science and Technology Development Fund Project (20171006).

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Author notes

  1. Ye Shen and Lianming Zhou contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, Shanghai Fengxian District Central Hospital, No. 6600 Nanfeng Road, Fengxian District, Shanghai, 201499, China

    Ye Shen, Lianming Zhou, Meiyu Xu, Zhanhai Tan, Kai Yao & Wenjie Wang

Authors
  1. Ye Shen
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  2. Lianming Zhou
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  3. Meiyu Xu
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  4. Zhanhai Tan
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  5. Kai Yao
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  6. Wenjie Wang
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Contributions

Dr YS and LMZ contributed to the study design. MYX conducted the literature search. MYX and ZHT acquired the data. YS and LMZ wrote the article. ZHT and KY performed data analysis. WJW revised the article and gave the final approval of the version to be submitted. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Wenjie Wang.

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Shen, Y., Zhou, L., Xu, M. et al. MED1 induces M2 polarization of tumor-associated macrophages to aggravate breast cancer. Genes Genom 45, 1517–1525 (2023). https://doi.org/10.1007/s13258-023-01435-0

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