Second, extracellular HMGB1 induced caspase-1 activation through RAGE and TLR4 pathways to increase the expression of multiple inflammatory mediators, which could promote metastasis and invasion of cancer cells [12, 13] and lastly, HMGB1 was also involved in endothelium cell (EC) activation and angiogenic activity through the MAPK, ERK and JNK pathways, acting as a proangiogenic cytokine [14, 46]. Here, MAPK8 is linked to cancer.