Macrophage ERα promoted invasion of endometrial cancer cell by mTOR/KIF5B -mediated epithelial to mesenchymal transition.

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 first identified that 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 CCL18, and its expression promoted the invasion of endometrial cancer cells by activating the ERK1/2 pathway, whereas suppressing CCL18 abrogated these effects. Furthermore, we initially 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. This article is protected by copyright. All rights reserved.