Crosstalk of Hippo signal pathway with other signaling pathways to regulate YAP1

Crosstalk of Hippo signal pathway with other signaling pathways to regulate YAP1. When Hippo signaling is active, MST1/2 kinase phosphorylates the SAV1 complex, which then activates LATS1/2 and its regulatory protein MOB1/2 complex. Subsequently, LATS1/2 phosphorylates YAP1 at a highly conserved residue within a specific sequence. Phosphorylation at Ser-127 promotes cytoplasmic retention of YAP1, while phosphorylation at Ser-397 induces degradation. In the absence of Hippo pathway activity, YAP1 is dephosphorylated and translocates into the nucleus. There, YAP1 binds to and activates TEAD transcription factors, promoting the expression of genes such as CTGF and CYR61. The Wnt, MAPK, PI3K, EMT, Notch, EGFR, TNF, cAMP and HGF/c-MET signaling pathways affect the expression of YAP1 in tumor cells. X indicates inhibition. YAP1, yes-associated protein 1; MST1/2, mammalian STE20-like 1/2; SAV1, salvador homologue 1; LATS1/2, large tumor suppressor 1/2; TEAD, TEA domain family member; MOB1, MOB kinase activator 1; CTGF, connective tissue growth factor; CYR61, cysteine-rich angiogenic inducer 61; EMT, epithelial mesenchymal transition; HGF, hepatocyte growth factor; cAMP, cyclic adenosine monophosphate

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Targeting the Hippo/YAP1 signaling pathway in hepatocellular carcinoma: From mechanisms to therapeutic drugs (Review) (2024) Shenghao Li, et al. Int J Oncol. 2024 Sep;65(3). Figure: F3. Homo sapiens

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