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

Abstract

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. The present study intended to explore the role of MED1 in macrophage polarization and its further influence on the malignant behaviors of breast cancer. 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. 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. In summary, MED1 could induce M2 macrophage polarization and thus regulate the malignant behaviors of breast cancer cells.