Intratumoral Fusobacterium nucleatum drives ferroptosis resistance and a disulfide-stress vulnerability

Research shows that infection with Fusobacterium nucleatum (Fn) inside tumors raises expression of the transporter SLC7A11, blunting ferroptosis induced by agents such as erastin and RSL3. When glucose is plentiful, infected cells are therefore relatively resistant to this form of cell death. Hydrogen sulfide generated during Fn infection appears to underpin the SLC7A11 increase and the downstream glutathione/GPX4 axis response, accompanied by reduced lipid-peroxide and ferrous iron (Fe2+) accumulation, lower ACSL4 levels and higher FTH1 levels. Under glucose restriction, however, the same Fn-driven state creates a distinct disulfide-stress-associated vulnerability. The mechanistic links between bacterial metabolism, SLC7A11, the antioxidant axis and the ferroptosis machinery are still being mapped out, and therapeutic implications remain to be established.

Written by a model from the reports · updated 3 hours ago