乳腺癌是世界上最常见的肿瘤之一，转移是肿瘤相关死亡的主要原因。肿瘤相关巨噬细胞（TAM）是肿瘤微环境（TME）的主要组成部分，通常与癌症转移相关。然而，TAM 调节乳腺癌转移的机制仍不清楚。在这项研究中，我们发现转谷氨酰胺酶 2 (TGM2) 可以作为调节 TAM 诱导的上皮间质转化 (EMT) 和乳腺癌细胞侵袭的关键靶标。进一步分析发现，TAMs分泌IL-6，能够通过激活JAK/STAT3信号通路诱导TGM2表达。随后的荧光素酶报告基因检测表明 STAT3 与 TGM2 启动子区域结合，从而在转录上增强 TGM2 表达。总之，我们目前的研究已确定 IL-6/STAT3/TGM2 轴是 TAM 引起的乳腺肿瘤发生的关键调节因子，为乳腺癌的治疗提供了一个新靶点。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Breast cancer is one of the most common tumors in the world and metastasis is the major cause of tumor-related death. Tumor-associated macrophages (TAMs) are a major component of the tumor microenvironment (TME) and often associated with cancer metastasis. Nevertheless, the mechanism by which TAMs regulate breast cancer metastasis remain unclear. In this study, we found that transglutaminase 2 (TGM2) could serve as a crucial target in the modulation of TAMs-induced epithelial-mesenchymal transition (EMT) and invasion of breast cancer cells. Further analysis revealed that IL-6 secreted from TAMs, which was capable of inducing TGM2 expression through the activation of the JAK/STAT3 signaling pathway. Subsequent luciferase reporter assays demonstrated that STAT3 binds to the TGM2 promoter region, thereby transcriptionally enhancing TGM2 expression. In conclusion, our current research has identified the IL-6/STAT3/TGM2 axis as a pivotal regulator in breast tumorigenesis caused by TAMs, presenting a novel target for the treatment of breast cancer.Copyright © 2024 Elsevier B.V. All rights reserved.