Skip to main content


Fig. 2 | Molecular Cancer

Fig. 2

From: Function of the c-Met receptor tyrosine kinase in carcinogenesis and associated therapeutic opportunities

Fig. 2

Illustration of the molecular mechanism of c-Met downstream signaling pathways. a Binding of HGF and c-Met can induce conformational changes in c-Met, resulting in the activation of downstream Ras-Raf-MAPK and PI3K/AKT/mTOR signaling pathways. After autophosphorylation, PTK binds Gab2 and activates it. Gab2 activates SOS; SOS activates Ras and then Ras stimulates Raf, MEK, and MAPKs. Activated MAPKs can enter the nucleus to regulate the expression of transcription factors such as Elk1, Etsl, and c-Myc (among others) to modulate cell proliferation and apoptosis. b The PTK domain is the site of autophosphorylation and also provides a docking site for PI3K. With this interaction, PI3K converts PIP2 to PIP3, and then PIP3 binds to the signaling proteins AKT and PDK1; PDK activates AKT, and activated AKT not only translocates to the nucleus, but also activates GSK-3 and mTOR to regulate the expression of multiple transcription factors. c Wnt binds to the low-density lipoprotein receptor-related protein 5/6/Frizzled (LRP5/LRP6/Frizzled) co-receptor group and activates the Dishevelled protein (DSH/Dvl) resulting in inhibition of the degradation of β-catenin by the destruction complex (consisting of Axin, adenomatosis polyposis coli (APC), protein phosphatase 2A (PP2A), glycogen synthase kinase 3 (GSK3) and casein kinase 1α (CK1α)).Subsequently, β-catenin is transported to the nucleus via Rac1 and other factors and binds to the LEF/TCF transcription factors in the nucleus with BCL9/LGS and Pygo to promote expression of oncogenes such as Myc, Cyclin D1, and MMP-7. This process can promote the invasion and migration of cancer cells. Aberrant activation of HGF/c-Met in tumor cells can block the degradation of β-catenin by the destruction complex, resulting in a higher concentration of β-catenin in the cytoplasm, and can also promote the entry of β-catenin into the nucleus

Back to article page