A GPX1-OSBPL8 axis mediates noncanonical in vivo ferroptosis and cancer growth suppression - PubMed
2 days ago
- #ROS
- #cancer
- #ferroptosis
- Ferroptosis is a tumor-suppressive mechanism with therapeutic potential.
- Canonical ferroptosis is triggered by inducers like erastin, RSL-3, or GPX4 loss, but natural in vivo ferroptosis mechanisms were unclear.
- A noncanonical ferroptosis pathway is driven by ROS-induced phosphatidic acid (PA) peroxidation, independent of inducers.
- GPX1 regulates ROS-induced ferroptosis by modulating PA peroxidation, with its effects dependent on OSBPL8.
- ROS-driven lipid peroxidation accumulates at the ER before cell death; GPX1 is recruited to the ER via OSBPL8 to reduce oxidized PA.
- GPX1 and OSBPL8 are overexpressed in cancers; their knockdown promotes ferroptosis and suppresses tumor growth.
- The study links the GPX1-OSBPL8 axis to in vivo ferroptosis and tumor suppression.