MAPK3 and cancer: Extracellular succinate activated the PI3K-Akt pathway by combining SUCNR1 in tumor cells and upregulating HIF-1α, promoting cancer cell invasion and driving epithelial–mesenchymal.36–38 In gastric cancer, it was found that succinate could activate it via the SUCNR1-ERK1/2-STAT3-VEGF pathway leading to the angiogenesis.39 Besides driving cancer cell migration, extracellular succinate significantly impacts macrophages within the tumor microenvironment.