Fig. 2: Key ferroptosis targets in GBM: ferroptosis is closely linked to lipid ROS production, which is regulated by both GPX4 levels and iron metabolism.
From: Ioning out glioblastoma: ferroptosis mechanisms and therapeutic frontiers
In iron regulation, TRIM7 and COPZ1 suppress iron-related protein expression or activity, reducing cellular iron levels, whereas the IRP/IRE pathway inhibits ferritin degradation, leading to iron accumulation. In GPX4-related regulation, APOC1 enhances GSH levels to promote GPX4 synthesis, while the NF-κB pathway synergistically amplifies ferroptosis under GPX4-deficient conditions. Furthermore, ACSL4 drives AA-CoA/ADA-CoA generation, and circLRFN5 elevates lipid ROS by suppressing the PRRX2/GCH1/BH4 axis. Together, these mechanisms collectively promote ferroptosis in GBM.
