Nevertheless, the existence of death-ligand-independent modes of caspase-8 activation was already revealed in other cell types: e.g., ER stress-induced CHOP activation by PA application in human hepatoma cells was shown to transcriptionally upregulate DR5, which subsequently resulted in ligand-independent caspase-8 activation by this death receptor [268]. The gene discussed is CASP8; the disease is hepatocellular carcinoma.