HMGB1 and hepatocellular carcinoma: In a different study, Yan et al. showed that in HCC cells exposed to hypoxia, HMGB1 secreted extracellularly interacted with both TLR-4 and RAGE to promote cellular invasion through the activation of caspase 1, resulting in the cleavage and subsequent activation of the pro-inflammatory cytokines IL-1β and IL-18 [179].