%0 Journal Article
%T RANKL/RANK signaling recruits Tregs via the CCL20-CCR6 pathway and promotes stemness and metastasis in colorectal cancer.
%A Ouyang J
%A Hu S
%A Zhu Q
%A Li C
%A Kang T
%A Xie W
%A Wang Y
%A Li Y
%A Lu Y
%A Qi J
%A Xia M
%A Chen J
%A Yang Y
%A Sun Y
%A Gao T
%A Ye L
%A Liang Q
%A Pan Y
%A Zhu C
%J Cell Death Dis
%V 15
%N 6
%D 2024 Jun 20
%M 38902257
暂无%R 10.1038/s41419-024-06806-3
%X 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.