癌症研究
上皮-间质转换
子宫内膜癌
PI3K/AKT/mTOR通路
雌激素受体
趋化因子
蛋白激酶B
CCL18型
肿瘤相关巨噬细胞
细胞生物学
癌症
化学
信号转导
生物
医学
炎症
内科学
转移
乳腺癌
作者
Xinxin Jing,Jin Peng,Dou Yu,Jia Sun,Caihong Ma,Qingjie Wang,Lin Zhang,Xia Luo,Beihua Kong,Yun Zhang,Lijie Wang,Xun Qu
摘要
Abstract Tumor‐associated macrophages (TAMs) exert tumor‐promoting effects. There have been reports that estrogen receptors (ERs) are expressed on the infiltrating macrophages of endometriosis, ovarian cancer and lung cancer. However, the role of ERs in macrophages is not well characterized. In this study, we identified that ER alpha (ERα) expression on the macrophages of human endometrial cancer was positively correlated with cancer progression. Conditioned medium from selective ERα agonist‐treated M2 macrophages induced the epithelial to mesenchymal transition (EMT) in endometrial cancer cells. However, this effect can be inhibited by ERα antagonist. Here, we showed that macrophages ERα‐engaged abundantly produced chemokine (C‐C motif) ligand 18 (CCL18), and its expression promoted the invasion of endometrial cancer cells by activating the extracellular signal‐regulated kinase 1/2 pathway, whereas suppressing CCL18 abrogated these effects. Furthermore, we identified that CCL18 derived from TAMs upregulated KIF5B expression to promote EMT via activating the PI3K/AKT/mTOR signaling pathway in endometrial cancer. Overall, our findings show how ERα‐engaged infiltrating macrophages initiate chronic inflammation and promote the aggressive progression of endometrial cancer cells. ERα‐positive TAMs act as drivers of endometrial cancer, which may become a potential therapeutic target.
科研通智能强力驱动
Strongly Powered by AbleSci AI