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.

Details

Title
RANKL/RANK signaling recruits Tregs via the CCL20–CCR6 pathway and promotes stemness and metastasis in colorectal cancer
Author
Ouyang, Jing 1 ; Hu, Shuang 2 ; Zhu, Qingqing 1 ; Li, Chenxin 1 ; Kang, Tingting 1 ; Xie, Wenlin 3 ; Wang, Yun 1 ; Li, Yan 1 ; Lu, Yingsi 1 ; Qi, Junhua 4 ; Xia, Ming 1 ; Chen, Jinrun 1 ; Yang, Yingqian 1 ; Sun, Yazhou 5 ; Gao, Tianshun 5 ; Ye, Liping 1   VIAFID ORCID Logo  ; Liang, Qian 6 ; Pan, Yihang 1 ; Zhu, Chengming 1   VIAFID ORCID Logo 

1  Sun Yat-sen University, Scientific Research Center, The Seventh Affiliated Hospital, Shenzhen, China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X); Guangdong Provincial Key Laboratory of Digestive Cancer Research, Shenzhen, China (GRID:grid.12981.33) 
2  The First Affiliated Hospital of Zhengzhou University, Department of Oncology, Zhengzhou, China (GRID:grid.412633.1) 
3  Sun Yat-sen University, Pathological Diagnostic Center, The Seventh Affiliated Hospital, Shenzhen, China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X) 
4  Sun Yat-sen University, Department of Clinical Medical Laboratory, The Seventh Affiliated Hospital, Shenzhen, China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X) 
5  Sun Yat-sen University, Scientific Research Center, The Seventh Affiliated Hospital, Shenzhen, China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X); Guangdong Provincial Key Laboratory of Digestive Cancer Research, Shenzhen, China (GRID:grid.12981.33); Sun Yat-sen University, Clinical Big Data Research Center, The Seventh Affiliated Hospital, Shenzhen, China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X) 
6  The Shenzhen Second People’s Hospital, Department of Spine Surgery, The First Affiliated Hospital of Shenzhen University, Shenzhen, China (GRID:grid.452847.8) (ISNI:0000 0004 6068 028X) 
Pages
437
Publication year
2024
Publication date
Jun 2024
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41419-024-06806-3
ProQuest document ID
3070126601
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.