Targeting YAP in pancreatic ductal adenocarcinoma (PDAC) (WP5495)
Homo sapiens
"Targeting YAP for PDAC therapy. There are several strategies for targeting YAP in PDAC. Statin-mediated inhibition of HMG-CoA reductase in the mevalonate pathway reduces the geranylgeranylation and membrane localization of Rho GTPases, restricting YAP nuclear accumulation and thus its activity. Verteporfin and VGLL4-mimicking peptides disrupt the interaction between YAP and TEAD, inhibiting YAP-induced transcription. Metformin activates AMPK, which inhibits YAP both directly and by activating LATS kinases. BET inhibitors oppose the transcription of YAP-regulated genes. Neratinib increases the phosphorylation of LATS1 and YAP, causing YAP cytosolic accumulation and degradation." Based on Figure F5 in https://pubmed.ncbi.nlm.nih.gov/33408779/. Derived from PFOCR, https://pfocr.wikipathways.org/figures/PMC7778590__thnov11p1753g005.html.
Authors
Eric WeitzActivity
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Organisms
Homo sapiensCommunities
Annotations
Pathway Ontology
drug pathwayDisease Ontology
pancreatic ductal adenocarcinomaCell Type Ontology
pancreatic ductal cell| Label | Type | Compact URI | Comment |
|---|---|---|---|
| Neratinib | Metabolite | chebi:61397 | |
| Verteporfin | Metabolite | chebi:32293 | |
| Atorvastatin | Metabolite | chebi:39548 | |
| Fluvastatin | Metabolite | chebi:38561 | |
| Lovastatin | Metabolite | chebi:40303 | |
| Pitavastatin | Metabolite | chebi:32020 | |
| Pravastatin | Metabolite | chebi:63618 | |
| Rosuvastatin | Metabolite | chebi:38545 | |
| Simvastatin | Metabolite | chebi:9150 | |
| HMG-CoA | Metabolite | chebi:15467 | |
| Mevalonic acid | Metabolite | chebi:25351 | |
| Metformin | Metabolite | chebi:6801 | |
| STK3 | GeneProduct | ensembl:ENSG00000104375 | |
| STK4 | GeneProduct | ensembl:ENSG00000101109 | |
| SAV1 | GeneProduct | ensembl:ENSG00000151748 | |
| LATS1 | GeneProduct | ensembl:ENSG00000131023 | |
| LATS2 | GeneProduct | ensembl:ENSG00000150457 | |
| PRKAA1 | GeneProduct | ensembl:ENSG00000132356 | |
| PRKAA2 | GeneProduct | ensembl:ENSG00000162409 | |
| PRKAB1 | GeneProduct | ensembl:ENSG00000111725 | |
| PRKAB2 | GeneProduct | ensembl:ENSG00000131791 | |
| PRKAG1 | GeneProduct | ensembl:ENSG00000181929 | |
| PRKAG2 | GeneProduct | ensembl:ENSG00000106617 | |
| PRKAG3 | GeneProduct | ensembl:ENSG00000115592 | |
| YAP1 | GeneProduct | ensembl:ENSG00000137693 | |
| RHO | GeneProduct | ensembl:ENSG00000163914 | |
| RHOD | GeneProduct | ensembl:ENSG00000173156 | |
| RHOA | GeneProduct | ensembl:ENSG00000067560 | |
| RHOB | GeneProduct | ensembl:ENSG00000143878 | |
| RHOC | GeneProduct | ensembl:ENSG00000155366 | |
| MOB1A | GeneProduct | ensembl:ENSG00000114978 | |
| HMGCR | GeneProduct | ensembl:ENSG00000113161 | 'HMG-CoA reductase' originally |
| TEAD1 | GeneProduct | ensembl:ENSG00000187079 | |
| TEAD2 | GeneProduct | ensembl:ENSG00000074219 | |
| TEAD3 | GeneProduct | ensembl:ENSG00000007866 | |
| TEAD4 | GeneProduct | ensembl:ENSG00000197905 | |
| CCN2 | GeneProduct | ensembl:ENSG00000118523 | |
| CCN1 | GeneProduct | ensembl:ENSG00000142871 |
References
- YAP in pancreatic cancer: oncogenic role and therapeutic strategy. Mao W, Mai J, Peng H, Wan J, Sun T. Theranostics. 2021 Jan 1;11(4):1753–62. PubMed Europe PMC Scholia