Furthermore, HMGB1 and RAGE interaction activates MAPK signaling pathway through K-Ras, Rac1/JNK/SAPK, and ERK1/2/Drp1 phosphorylation and prompts CRC progression, chemoresistance and regrowth of cancer cells, and colonic myofibroblast proliferation, migration, and invasion (57, 156, 163, 164). This evidence concerns the gene AGER and cancer.