RANKL/RANK signaling recruits Tregs via the CCL20-CCR6 pathway and promotes stemness and metastasis in colorectal cancer.
Cell Death Dis
; 15(6): 437, 2024 Jun 20.
Article
em En
| MEDLINE
| ID: mdl-38902257
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
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Neoplasias Colorretais
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Transdução de Sinais
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Linfócitos T Reguladores
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Ligante RANK
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Receptor Ativador de Fator Nuclear kappa-B
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Quimiocina CCL20
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Receptores CCR6
Limite:
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cell Death Dis
Ano de publicação:
2024
Tipo de documento:
Article