CASP1
Overview
CASP1 (Caspase 1) encodes an inflammatory cysteine protease that is a key mediator of pyroptosis and IL-1β processing. CASP1 is part of a caspase locus on chromosome 11q22-23 alongside CASP4, CASP5, and CASP12. Loss of caspase-mediated apoptotic signaling can provide tumor cells with survival advantages, and genomic deletion at this locus has been observed in hepatocellular carcinoma.
Alterations observed in the corpus
- Loss of copy number at the caspase locus (CASP1, CASP4, CASP5, CASP12) observed in 10% of liver cancer samples, inhibiting apoptosis PMID:22634756
Cancer types (linked)
- HCC (hepatocellular carcinoma): Copy number loss at the caspase locus in ~10% of cases; the concurrent deletion of multiple caspase genes at this locus likely provides a combined anti-apoptotic effect PMID:22634756
Co-occurrence and mutual exclusivity
- Copy number loss co-occurs with CTNNB1 pathway activation and HBV integration events in HCC; the locus deletion encompasses CASP4, CASP5, and CASP12 as a cluster PMID:22634756
Therapeutic relevance
- Loss of caspase-mediated apoptotic capacity in HCC could confer resistance to apoptosis-inducing therapies; strategies to restore caspase signaling or exploit pyroptosis pathways are under investigation.
Open questions
- Whether CASP1 loss alone or the entire caspase locus deletion is the key oncogenic event at 11q22-23 in HCC remains unclear.
Sources
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