HMGB1 through pyroptosis mediated by GSDME in epithelial cells, binds to RAGE and activates the extracellular regulated protein kinases (ERK1/2) signaling increasing cell migration by activating Rac1 and Cdc42.228 It has been reported that an elevated HMGB1 level is associated with invasion and metastasis in many cancer types. This evidence concerns the gene HMGB1 and cancer.