SLC39A8 Inhibits Ferroptosis by Regulating the Β-Catenin/TCF4/ GPX4 Signaling in Osteosarcoma

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• SLC39A8's role in osteosarcoma (OS) is not well understood.
• This study investigates the functional significance of SLC39A8 in OS progression.

Purpose of the Study:

• To elucidate the role of SLC39A8 in osteosarcoma (OS) progression.
• To investigate the underlying molecular mechanisms, including ferroptosis and Wnt/β-catenin signaling.

Main Methods:

• Analyzed SLC39A8 expression in OS cells using qRT-PCR and Western blot.
• Assessed cell proliferation, migration, and invasion via CCK-8, colony formation, and transwell assays.
• Evaluated ferroptosis by measuring key biomarkers and assessing the impact of SLC39A8 modulation and ferroptosis inhibitors.

Main Results:

• SLC39A8 was upregulated in OS cells and promoted proliferation, migration, and invasion.
• SLC39A8 knockdown induced ferroptosis, evidenced by altered lipid peroxidation, iron levels, ROS, GSH, and GPX4 expression.
• SLC39A8 activated Wnt/β-catenin signaling, which was crucial for its effects on GPX4 and ferroptosis. In vivo studies confirmed tumor growth inhibition upon SLC39A8 knockdown.

Conclusions:

• SLC39A8 promotes OS progression by suppressing ferroptosis via the β-catenin/TCF4/GPX4 signaling pathway.
• SLC39A8 acts as a key regulator of iron metabolism and ferroptosis in osteosarcoma.
• Targeting SLC39A8 may represent a novel therapeutic strategy for osteosarcoma.