Figure 4.

The main signaling pathways in the progression phase of LR

Extracellular signal activates LATS1/2 by a complex Mst1/2 kinase and SAV1, which enables YAP/TAZ to be transported to the nucleus and interact with TEAD1-4 and other transcription factors. When pro-HGF is activated by u-PA, it can bind to c-Met to initiate a variety of downstream signaling pathways, including ERK1/2 signaling pathway and PI3K/AKT signaling pathway. When ligand-receptor binding or the PI3K/AKT signaling pathway is stimulated, PI3K promotes the conversion of from PIP2 to PIP3. PIP3 can act on AKT directly or through PDK1 on AKT, thereby activating mTOR. TEAD, Transcriptional enhanced associate domain; PIP2, Phosphatidylinositol 4, 5-diphosphate; PIP3, Phosphatidylinositol 3,4, 5-triphosphate; PDK1, 3-phosphate dependent protein kinase 1.