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- Title
RANKL/RANK signaling recruits Tregs via the CCL20–CCR6 pathway and promotes stemness and metastasis in colorectal cancer.
- Authors
Ouyang, Jing; Hu, Shuang; Zhu, Qingqing; Li, Chenxin; Kang, Tingting; Xie, Wenlin; Wang, Yun; Li, Yan; Lu, Yingsi; Qi, Junhua; Xia, Ming; Chen, Jinrun; Yang, Yingqian; Sun, Yazhou; Gao, Tianshun; Ye, Liping; Liang, Qian; Pan, Yihang; Zhu, Chengming
- Abstract
TNF receptor superfamily member 11a (TNFRSF11a, RANK) and its ligand TNF superfamily member 11 (TNFRSF11, RANKL) are overexpressed in many malignancies. However, the clinical importance of RANKL/RANK in colorectal cancer (CRC) is mainly unknown. We examined CRC samples and found that RANKL/RANK was elevated in CRC tissues compared with nearby normal tissues. A higher RANKL/RANK expression was associated with a worse survival rate. Furthermore, RANKL was mostly produced by regulatory T cells (Tregs), which were able to promote CRC advancement. Overexpression of RANK or addition of RANKL significantly increased the stemness and migration of CRC cells. Furthermore, RANKL/RANK signaling stimulated C-C motif chemokine ligand 20 (CCL20) production by CRC cells, leading to Treg recruitment and boosting tumor stemness and malignant progression. This recruitment process was accomplished by CCL20–CCR6 interaction, demonstrating a connection between CRC cells and immune cells. These findings suggest an important role of RANKL/RANK in CRC progression, offering a potential target for CRC prevention and therapy.
- Publication
Cell Death & Disease, 2024, Vol 15, Issue 6, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/s41419-024-06806-3