Study links ER remodeling to cancer cell pyroptosis

A recent study from Peking University has identified a new mechanism linking endoplasmic reticulum (ER) membrane remodeling to pyroptosis, a type of inflammatory cell death relevant to cancer treatment. Researchers found that targeting reticulon-4 (RTN4) can induce pyroptosis in cancer cells. Using a chemical probe, α-mangostin, the study showed that RTN4 degradation leads to significant changes in ER structure, promoting the formation of pyroptotic cell features. This process activates the caspase-3/GSDME pathway, enhancing immune responses and inhibiting tumor growth. The findings suggest that RTN4 is a potential target for cancer therapies. The study indicates that small molecules like α-mangostin could be developed to enhance antitumor immunity, especially when used alongside existing treatments like anti-PD-1 therapy.