CASP4 Cancer Research Results

CASP4 - Caspase 4

Abbreviation: CASP4, Caspase-4

Type: Inflammatory caspase / cysteine protease / noncanonical inflammasome mediator / pyroptosis regulator

Function: Caspase-4 is a human inflammatory caspase that directly senses cytosolic lipopolysaccharide (LPS) and activates the noncanonical inflammasome pathway. Activated caspase-4 cleaves gasdermin D (GSDMD), generating the pore-forming GSDMD N-terminal fragment and promoting pyroptotic cell death. Caspase-4-mediated potassium efflux can also activate the NLRP3-caspase-1 pathway and enhance inflammatory cytokine release.

Cancer: ↕ Context-dependent. ↑ Caspase-4 activity can promote pyroptotic death of cancer cells and enhance antitumor immune responses. However, chronic caspase-4-dependent inflammation and pyroptosis-associated cytokine release can also create a tumor-promoting inflammatory microenvironment in some cancers.

Favorable Direction in Cancer: Context-dependent. ↑ CASP4 activity can be favorable when it induces tumor-cell pyroptosis, whereas ↓ CASP4-associated inflammatory signaling may be favorable where chronic inflammation promotes tumor progression.

Interpretation Note: Caspase-4 is distinct from apoptotic executioner caspases such as CASP3 and CASP7. In humans, CASP4 and CASP5 mediate noncanonical inflammasome signaling; murine CASP11 is the functional counterpart.