Gastric cancer-cell derived EVs carrying high mobility group box-1 (HMGB1) bind with TLR or receptor for advanced glycation end products (RAGE) to activate NF-κB signaling, which induces the phosphorylation of downstream proteins including p65, STAT, and ERK and upregulates the expression of inflammatory factors such as IL-1β, IL-6, IL-8, OSM, and TNFα (Figure 2). Here, HMGB1 is linked to gastric cancer.