Table I.
Gene and drug therapies targeting the Hippo signaling pathway.
| Gene and drug therapies | Hippo target | Mechanisms | (Refs.) |
|---|---|---|---|
| RASSF6, DLG5 | MST1/2 and LATS1 | Promotes the phosphorylation of MST1/2 and LATS1 | (24,25) |
| MARK4 | MST and SAV | Weakens the formation of the MST-SAV and LATS complex | (11) |
| MAC30 | MST1/2 and LATS1/2 | Attenuates MST1/2 and LATS1/2 levels | (26) |
| Neoadjuvant therapy | MST1/2 | Activates the nuclear localization of pMST1/2 | (12) |
| VEGF | LATS1/2 | Activates GTPase Rac1, thereby inhibiting LATS | (28) |
| Resveratrol | LATS1 | Activates LATS1 | (29) |
| BRCA1 | NF2 | Contributes to the inactivation of the Hippo signaling pathway through NF2 ubiquitination | (30) |
| CRL4DCAF1, Itch | LATS1/2 | Ubiquitylates and inhibits LATS1/2 | (31) |
| SIAH2 | LATS1/2 | Inactivates LATS1/2 via proteases | (33) |
| USP9X | LATS | Interacts with LATS kinase and enhances the stability of LATS | (34) |
| LIFR | YAP | Promotes YAP phosphorylation and cytoplasmic retention | (35) |
| FAT1 | YAP/TAZ | The loss of FAT1 promotes YAP/TAZ expression | (36) |
| SPCA2, ERK1 | YAP/TAZ | Activates YAP/TAZ expression | (37,38) |
| EPI and NE | YAP1 | Through YAP1 phosphorylation and cytoplasmic retention | (39) |
| RNF187 | YAP1 | Polyubiquitinates and degrades YAP1 | (40) |
| OTUB2 | YAP/TAZ | Deubiquitinates and activates YAP/TAZ | (41) |
RASSF6, Ras association domain-containing protein 6; DLG5, discs large homolog 5; MARK4, microtubule affinity regulating Kinase 4; MAC30, meningioma-associated protein; VEGF, vascular endothelial growth factor; BRCA1, breast cancer type 1 susceptibility protein; LIFR, leukemia inhibitory factor receptor; FAT1, FAT atypical cadherin 1; SPCA2, Ca2+-ATPase isoform 2; ERK1, extracellular regulated protein kinase 1; EPI, epinephrine; NE, norepinephrine; MST1/2, upstream sterile 20-like kinase 1 and 2; LATS1/2, large tumor suppressors 1 and 2; YAP, Yes-associated protein; TAZ, transcriptional coactivator with PDZ-binding motif; SAV, Salvador homologue; NF2, neurofibromatosis type 2.