Figure 5.

GSDME^NT switches apoptosis to secondary necrosis/pyroptosis. (a) Caspase‐3, which is activated by intrinsic or extrinsic apoptotic pathway, cleaves GSDME to generate the pyroptotic GSDME^NT fragment, which permeabilises the plasma membrane and releases pro‐inflammatory DAMP molecules such as HMGB1, finally leading to secondary necrosis in macrophages. (b) Caspase‐3, which is activated by intrinsic or extrinsic apoptotic pathway, mediates GSDME cleavage to generate the pyroptotic GSDME^NT fragment, which permeabilises the plasma membrane and releases LDH, finally leading to pyroptosis in cancer cells. CASP‐3, caspase‐3; Cyt c, cytochrome c; DAMP, danger‐associated molecular pattern; HMGB1, high mobility group box 1; LDH, lactate dehydrogenase.