RANK/RANKL axis promotes migration, invasion, and metastasis of osteosarcoma via activating NF-κB pathway

• Published in: Experimental cell research 2024-03, Vol.436 (2), p.113978-113978, Article 113978
• Main Authors: Takeda, Tomoya, Tsubaki, Masanobu, Genno, Shuji, Tomita, Kana, Nishida, Shozo
• Format: Article
• Language: English
• Subjects: Dimethyl fumarate; DMF; EMT; Epithelial-mesenchymal transition; Lung metastasis; NF-κB; Nuclear factor-kappa B; OS; Osteosarcoma; RANK; Receptor activator of nuclear factor kappa-B
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2024.113978

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. •RANK/RANKL axis enhances aggressive behavior by promoting EMT in OS.•RANK/RANKL axis induces EMT by activating NF-κB pathway.•DMF suppresses migration, invasion, and EMT of OS cells by inhibiting NF-κB.