ArticleOncogene2021
Functional characterization of uveal melanoma oncogenes.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 69 citations in OpenAlex.
- Does the ERBB/EGF Signaling Network Serve as a Nexus for Oncogenic Signals in Uveal Melanoma?Biomolecules · 2026Review
- Matched sampling reveals uncoupled phenotypic plasticity during metastasis formation in uveal melanoma.iScience · 2026Article
- Combination of Three Herbal Components (ISL, Que, Meth) Suppresses Uveal Melanoma Growth via Gαq/MEK/YAP Axis Modulation and Apoptosis.Biomedicines · 2026Article
- Precision Oncology in Ocular Melanoma: Integrating Molecular and Liquid Biopsy Biomarkers.Current issues in molecular biology · 2026Review
- Conserved Gαq-PLCβ-PKC signaling mediates trametinib resistance in BRAFbioRxiv : the preprint server for biology · 2025Article
- Inhibition of the RAC/PAK Signaling Axis Enhances the Potency of MAPK Cascade Inhibitors Against Uveal Melanoma.Biomolecules · 2025Article
- Mitfa-Independent Melanocyte Progenitors are Highly Susceptible to GNAQ-induced Uveal Melanoma in Adult Zebrafish.bioRxiv : the preprint server for biology · 2025Article
- The LINC01315-encoded small protein YAPer-ORF competes with PRP4k to hijack YAP signaling to aberrantly promote cell growth.Cell death and differentiation · 2025Article
- Super-enhancers orchestrate transcriptional dysregulation and metabolic reprogramming in uveal melanoma.Communications biology · 2025Article
- Decoding HSP90AA1-driven inflammatory signaling in the uveal melanoma microenvironment: an integrated analysis at single-cell resolution.Frontiers in immunology · 2025Article
- Exploring recent advances in signaling pathways and hallmarks of uveal melanoma: a comprehensive review.Exploration of targeted anti-tumor therapy · 2025Review
- GNAQ/GNA11-Related Benign and Malignant Entities-A Common Histoembriologic Origin or a Tissue-Dependent Coincidence.Cancers · 2024Review
- Genetic Features of Uveal Melanoma.Genes · 2024Review
- Systems modeling of oncogenic G-protein and GPCR signaling reveals unexpected differences in downstream pathway activation.NPJ systems biology and applications · 2024Article
- Review
- Endothelial EGLN3-PKM2 signaling induces the formation of acute astrocytic barrier to alleviate immune cell infiltration after subarachnoid hemorrhage.Fluids and barriers of the CNS · 2024Article
- INPP5A phosphatase is a synthetic lethal target in GNAQ and GNA11-mutant melanomas.Nature cancer · 2024Article
- Cooperative function of oncogenic MAPK signaling and the loss of Pten for melanoma migration through the formation of lamellipodia.Scientific reports · 2024Article
- The mechanism ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- High-throughput chemogenetic drug screening reveals PKC-RhoA/PKN as a targetable signaling vulnerability in GNAQ-driven uveal melanoma.Cell reports. Medicine · 2023Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Uveal melanoma (UM) is a currently untreatable form of melanoma with a 50% mortality rate. Characterization of the essential signaling pathways driving this cancer is critical to develop target therapies. Activating mutations in the Gαq signaling pathway at the level of GNAQ, GNA11, or rarely CYSLTR2 or PLCβ4 are considered alterations driving proliferation in UM and several other neoplastic disorders. Here, we systematically examined the oncogenic signaling output of various mutations recurrently identified in human tumors. We demonstrate that CYSLTR2 → GNAQ/11 → PLCβ act in a linear signaling cascade that, via protein kinase C (PKC), activates in parallel the MAP-kinase and FAK/Yes-associated protein pathways. Using genetic ablation and pharmacological inhibition, we show that the PKC/RasGRP3/MAPK signaling branch is the essential component that drives the proliferation of UM. Only inhibition of the MAPK branch but not the FAK branch synergizes with inhibition of the proximal cascade, providing a blueprint for combination therapy. All oncogenic signaling could be extinguished by the novel GNAQ/11 inhibitor YM-254890, in all UM cells with driver mutation in the Gαq subunit or the upstream receptor. Our findings highlight the GNAQ/11 → PLCβ → PKC → MAPK pathway as the central signaling axis to be suppressed pharmacologically to treat for neoplastic disorders with Gαq pathway mutations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.