CCL20 mediates RANK/RANKL-induced epithelial-mesenchymal transition in endometrial cancer cells

Abstract

RANK/RANKL facilitates migration/invasion via epithelial-mesenchymal transition (EMT) in certain malignant tumors. The relationship and mechanism between RANK/RANKL and EMT in endometrial cancer (EC) cells, however, remain unclear. In this study, we firstly showed that RANK/RANKL activation was correlated with EC staging and EMT markers in human EC tissue specimen. RANK/RANKL promoted migration/invasion and initiated EMT of EC cell lines. Then, protein chip analysis and enzyme-linked immunosorbent assay (ELISA) revealed that the expression and secretion of chemokine ligand 20 (CCL20) was dramatically enhanced in RANKL-treated RANK over-expressed EC cells. Moreover, the higher level of CCL20 in both serum and tumor tissue was detected in orthotopic transplantation mouse models. Finally, we confirmed that CCL20 contributed to invasion and EMT of RANK over-expressed EC cells. In summary, all data supported the hypothesis that RANK/RANKL elevated the expression and secretion of CCL20 in EC cells, which promoted cancer progression through EMT.