TLR4 and neoplasm: Glucose deprivation in tumor microenvironment is another stimulant of HMGB1 strong release of HMGB1 from several types of cancer cell lines under normal oxygen concentration, leading to activation of RAGE and TLR4, causing the activation of the MAPK/MEK1/2 and PI3K signaling pathways, leading to colonic myofibroblast migration and invasion (164).