RRC ID 78838
Author Takeda T, Tsubaki M, Genno S, Tomita K, Nishida S.
Title RANK/RANKL axis promotes migration, invasion, and metastasis of osteosarcoma via activating NF-κB pathway.
Journal Exp Cell Res
Abstract Osteosarcoma (OS) is one of the most prevalent primary bone tumors with a high degree of metastasis and poor prognosis. Epithelial-to-mesenchymal transition (EMT) is a cellular mechanism that contributes to the invasion and metastasis of cancer cells, and OS cells have been reported to exhibit EMT-like characteristics. Our previous studies have shown that the interaction between tumor necrosis factor superfamily member 11 (TNFRSF11A; also known as RANK) and its ligand TNFSF11 (also known as RANKL) promotes the EMT process in breast cancer cells. However, whether the interaction between RANK and RANKL enhances aggressive behavior by inducing EMT in OS cells has not yet been elucidated. In this study, we showed that the interaction between RANK and RANKL increased the migration, invasion, and metastasis of OS cells by promoting EMT. Importantly, we clarified that the RANK/RANKL axis induces EMT by activating the nuclear factor-kappa B (NF-κB) pathway. Furthermore, the NF-κB inhibitor dimethyl fumarate (DMF) suppressed migration, invasion, and EMT in OS cells. Our results suggest that the RANK/RANKL axis may serve as a potential tumor marker and promising therapeutic target for OS metastasis. Furthermore, DMF may have clinical applications in the treatment of lung metastasis in patients with OS.
Volume 436(2)
Pages 113978
Published 2024-3-15
DOI 10.1016/j.yexcr.2024.113978
PII S0014-4827(24)00069-7
PMID 38382805
MeSH Bone Neoplasms* / pathology Cell Line, Tumor Cell Movement / genetics Epithelial-Mesenchymal Transition / genetics Humans NF-kappa B / genetics NF-kappa B / metabolism Neoplasm Invasiveness Osteosarcoma* / pathology Receptor Activator of Nuclear Factor-kappa B / genetics Receptor Activator of Nuclear Factor-kappa B / metabolism Signal Transduction
Human and Animal Cells ST2(RCB0224)