2. Academic Validation
  3. RANKL/RANK signaling recruits Tregs via the CCL20-CCR6 pathway and promotes stemness and metastasis in colorectal cancer

RANKL/RANK signaling recruits Tregs via the CCL20-CCR6 pathway and promotes stemness and metastasis in colorectal cancer

  • Cell Death Dis. 2024 Jun 20;15(6):437. doi: 10.1038/s41419-024-06806-3.
Jing Ouyang 1 2,  Shuang Hu 3,  Qingqing Zhu 1 2,  Chenxin Li 1 2,  Tingting Kang 1 2,  Wenlin Xie 4,  Yun Wang 1 2,  Yan Li 1 2,  Yingsi Lu 1 2,  Junhua Qi 5,  Ming Xia 1 2,  Jinrun Chen 1 2,  Yingqian Yang 1 2,  Yazhou Sun 1 2 6,  Tianshun Gao 1 2 6,  Liping Ye 7 8,  Qian Liang 9,  Yihang Pan 10 11,  Chengming Zhu 12 13
Affiliations

Affiliations

  • 1 Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China.
  • 2 Guangdong Provincial Key Laboratory of Digestive Cancer Research, Shenzhen, 518107, Guangdong, China.
  • 3 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
  • 4 Pathological Diagnostic Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China.
  • 5 Department of Clinical Medical Laboratory, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China.
  • 6 Clinical Big Data Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China.
  • 7 Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China. yelp5@mail.sysu.edu.cn.
  • 8 Guangdong Provincial Key Laboratory of Digestive Cancer Research, Shenzhen, 518107, Guangdong, China. yelp5@mail.sysu.edu.cn.
  • 9 Department of Spine Surgery, The First Affiliated Hospital of Shenzhen University, The Shenzhen Second People's Hospital, Shenzhen, China. liangq2023spine@126.com.
  • 10 Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China. panyih@mail.sysu.edu.cn.
  • 11 Guangdong Provincial Key Laboratory of Digestive Cancer Research, Shenzhen, 518107, Guangdong, China. panyih@mail.sysu.edu.cn.
  • 12 Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China. zhuchm3@mail.sysu.edu.cn.
  • 13 Guangdong Provincial Key Laboratory of Digestive Cancer Research, Shenzhen, 518107, Guangdong, China. zhuchm3@mail.sysu.edu.cn.
PMID: 38902257 DOI: 10.1038/s41419-024-06806-3
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.

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