Inhibition of Gαq-regulated signaling in uveal melanoma (WP5490)
Homo sapiens
This pathway describes parallel and converging signaling pathways driven by Gαq (GNAQ) in Uveal Melanoma, and the inhibitory effects of Darovasertib and FAKi (FAK inhibitor). Key points from [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694608/ Arang et al]: Darovasertib is a dual inhibitor of PKC and PRK/PKN; downstream of mutant Gαq darovasertib blocks ERK and diminishes FAK activity; Darovasertib and FAKi act synergistically in preclinical uveal melanoma models. This pathway model was developed based on Figure 7 in [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694608/ Arang et al].
Authors
Kristina HanspersActivity
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Organisms
Homo sapiensCommunities
Annotations
Disease Ontology
uveal cancerPathway Ontology
G protein mediated signaling pathwayCell Type Ontology
melanocyte| Label | Type | Compact URI | Comment |
|---|---|---|---|
| FAK inhibitor | Metabolite | chebi:76617 | |
| DAG | Metabolite | chebi:18035 | |
| TEAD1 | GeneProduct | hgnc.symbol:TEAD1 | |
| PKC | GeneProduct | eccode:2.7.11.13 | |
| G-gamma | GeneProduct | interpro:IPR036284 | |
| GNAQ | GeneProduct | hgnc.symbol:GNAQ | |
| TSC1 | GeneProduct | ncbigene:7248 | |
| YAP1 | GeneProduct | hgnc.symbol:YAP1 | |
| FAK | GeneProduct | hgnc.symbol:PTK2 | |
| MTOR | GeneProduct | ncbigene:2475 | |
| PIK3CA | GeneProduct | ncbigene:5290 | |
| TRIO | GeneProduct | hgnc.symbol:TRIO | |
| RHOA | GeneProduct | hgnc.symbol:RHOA | |
| PKN1 | GeneProduct | hgnc.symbol:PKN1 | |
| ROCK1 | GeneProduct | hgnc.symbol:ROCK1 | |
| TEAD2 | GeneProduct | hgnc.symbol:TEAD2 | |
| TEAD3 | GeneProduct | hgnc.symbol:TEAD3 | |
| TEAD4 | GeneProduct | hgnc.symbol:TEAD4 | |
| PLCB1 | GeneProduct | hgnc.symbol:PLCB1 | |
| PLCB2 | GeneProduct | hgnc.symbol:PLCB2 | |
| PLCB3 | GeneProduct | hgnc.symbol:PLCB3 | |
| PLCB4 | GeneProduct | hgnc.symbol:PLCB4 | |
| MAPK1 | GeneProduct | hgnc.symbol:MAPK1 | |
| LATS1 | GeneProduct | hgnc.symbol:LATS1 | |
| LATS2 | GeneProduct | hgnc.symbol:LATS2 | |
| MOB1A | GeneProduct | hgnc.symbol:MOB1A | |
| PKN2 | GeneProduct | hgnc.symbol:PKN2 | |
| PKN3 | GeneProduct | hgnc.symbol:PKN3 | |
| G-beta | GeneProduct | interpro:IPR016346 | |
| AKT1 | GeneProduct | ncbigene:207 | |
| AKT2 | GeneProduct | ncbigene:208 | |
| AKT3 | GeneProduct | ncbigene:10000 | |
| TSC2 | GeneProduct | ncbigene:7249 | |
| PIK3CB | GeneProduct | ncbigene:5291 | |
| PIK3CD | GeneProduct | ncbigene:5293 | |
| PIK3R1 | GeneProduct | ncbigene:5295 | |
| PIK3R2 | GeneProduct | ncbigene:5296 | |
| PIK3R3 | GeneProduct | ncbigene:8503 |
References
- High-throughput chemogenetic drug screening reveals PKC-RhoA/PKN as a targetable signaling vulnerability in GNAQ-driven uveal melanoma. Arang N, Lubrano S, Ceribelli M, Rigiracciolo DC, Saddawi-Konefka R, Faraji F, et al. Cell Rep Med. 2023 Nov 21;4(11):101244. PubMed Europe PMC Scholia