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Canonical Mode of c-Met Activation Pattern The canonical mode of c-Met activation involves the binding of HGF to c-Met, which induces homodimerization and autophosphorylation of the cytoplasmic domain of c-Met and then triggers downstream signaling pathways, including the mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) (Gonzalez et al., 2017), phosphatidylinositol 3 kinase (PI3K) (Pascale et al., 2016), p-38 (Lee et al., 2003), and the Akt/protein kinase B (PKB) (Zhang et al., 2018c) pathways (Figure 2)