RANKL/RANK signaling recruits Tregs via the CCL20-CCR6 pathway and promotes stemness and metastasis in colorectal cancer.
Jing OuyangShuang HuQingqing ZhuChenxin LiTingting KangWenlin XieYun WangYan LiYingsi LuJunhua QiMing XiaJinrun ChenYingqian YangYazhou SunTianshun GaoLiping YeQian LiangYihang PanChengming ZhuPublished in: Cell death & disease (2024)
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.
Keyphrases
- bone loss
- nuclear factor
- regulatory t cells
- induced apoptosis
- cell cycle arrest
- stem cells
- dendritic cells
- gene expression
- rheumatoid arthritis
- epithelial mesenchymal transition
- toll like receptor
- cell death
- cell proliferation
- endoplasmic reticulum stress
- liver fibrosis
- climate change
- pi k akt
- immune response
- risk assessment
- smoking cessation
- cancer stem cells
- human health