Then, extracellular HMGB1 promotes the release of cytokines such as IL-6 and Tnf-α by activating MAPKs and Stat3 pathways, which stimulates tumor cells proliferation, angiogenesis, EMT, invasion, and metastasis (Chen Y. et al., 2016; Bailly, 2020). This evidence concerns the gene HMGB1 and neoplasm.