VAMP8 suppresses the metastasis via DDX5/β-catenin signal pathway in osteosarcoma

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Osteosarcoma is a bone cancer with high metastatic potential, requiring novel therapeutic strategies.
• Vesicle-associated membrane protein 8 (VAMP8) is implicated in various cancers, but its role in osteosarcoma metastasis is unknown.

Purpose of the Study:

• To investigate the functional role of VAMP8 in osteosarcoma metastasis.
• To elucidate the underlying molecular mechanisms of VAMP8's action in osteosarcoma.

Main Methods:

• Analysis of VAMP8 expression in osteosarcoma tissues and cells.
• Assessment of VAMP8's effect on osteosarcoma cell migration and invasion.
• Identification of VAMP8 interacting partners and investigation of downstream signaling pathways, including the ubiquitin-proteasome system, WNT/β-catenin signaling, and epithelial-mesenchymal transition (EMT).
• Evaluation of VAMP8's impact on autophagy flux.

Main Results:

• VAMP8 was significantly downregulated in osteosarcoma tissues and cells, correlating with poor patient prognosis.
• VAMP8 suppressed osteosarcoma cell migration and invasion.
• VAMP8 interacted with DDX5, promoting its proteasomal degradation, which led to reduced β-catenin levels and suppressed EMT.
• VAMP8 promoted autophagy flux, potentially contributing to metastasis suppression.

Conclusions:

• VAMP8 inhibits osteosarcoma metastasis through DDX5 proteasomal degradation, suppressing WNT/β-catenin signaling and EMT.
• VAMP8-mediated autophagy dysregulation may also play a role in suppressing osteosarcoma metastasis.
• Modulating VAMP8 presents a potential therapeutic strategy for targeting osteosarcoma metastasis.