ArticleThe Journal of biological chemistry2022
Oncogenic Gq/11 signaling acutely drives and chronically sustains metabolic reprogramming in uveal melanoma.
Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Redox Homeostasis, Metabolic Pathways and Plasticity in Uveal Melanoma Compared to Other Cancers.Cancers · 2026Review
- Loss of Gαq reshapes fibroblast traits and drives tumor-stroma remodeling in oral cancer progression.EMBO reports · 2026Article
- Allele-specific depletion ofMolecular therapy. Oncology · 2025Article
- The thiazolidinedione drug troglitazone inhibits Gq signaling through direct binding to the Gq alpha subunit through inhibition of GDP release.Molecular pharmacology · 2025Article
- Metabolic Inhibition Induces Pyroptosis in Uveal Melanoma.Molecular cancer research : MCR · 2025Article
- Identification of CKAP2 as a Potential Target for Prevention of Gastric Cancer Progression: A Multi-Omics Study.International journal of molecular sciences · 2025Article
- Hypoxia-induced BNIP3 facilitates the progression and metastasis of uveal melanoma by driving metabolic reprogramming.Autophagy · 2025Article
- The role of signaling pathways mediated by the GPCRs CysLTR1/2 in melanocyte proliferation and senescence.Science signaling · 2024Review
- Quercetin Impairs the Growth of Uveal Melanoma Cells by Interfering with Glucose Uptake and Metabolism.International journal of molecular sciences · 2024Article
- Recommended Tool Compounds: Application of YM-254890 and FR900359 to Interrogate GαACS pharmacology & translational science · 2023Review
- The Bacterial GJournal of chemical ecology · 2023Article
- The Effects of Oncological Treatment on Redox Balance in Patients with Uveal Melanoma.Diagnostics (Basel, Switzerland) · 2023Article
- Gq Signaling in Autophagy Control: Between Chemical and Mechanical Cues.Antioxidants (Basel, Switzerland) · 2022Review
- 1,4-dihydroxy quininib modulates the secretome of uveal melanoma tumour explants and a marker of oxidative phosphorylation in a metastatic xenograft model.Frontiers in medicine · 2022Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Metabolic reprogramming has been shown to occur in uveal melanoma (UM), the most common intraocular tumor in adults. Mechanisms driving metabolic reprogramming in UM are poorly understood. Elucidation of these mechanisms could inform development of new therapeutic strategies for metastatic UM, which has poor prognosis because existing therapies are ineffective. Here, we determined whether metabolic reprogramming is driven by constitutively active mutant α-subunits of the heterotrimeric G proteins Gq or G11 (Gq/11), the oncogenic drivers in ∼90% of UM patients. Using PET-computed tomography imaging, microphysiometry, and GC/MS, we found that inhibition of oncogenic Gq/11 with the small molecule FR900359 (FR) attenuated glucose uptake by UM cells in vivo and in vitro, blunted glycolysis and mitochondrial respiration in UM cell lines and tumor cells isolated from patients, and reduced levels of several glycolytic and tricarboxylic acid cycle intermediates. FR acutely inhibited glycolysis and respiration and chronically attenuated expression of genes in both metabolic processes. UM therefore differs from other melanomas that exhibit a classic Warburg effect. Metabolic reprogramming in UM cell lines and patient samples involved protein kinase C and extracellular signal-regulated protein kinase 1/2 signaling downstream of oncogenic Gq/11. Chronic administration of FR upregulated expression of genes involved in metabolite scavenging and redox homeostasis, potentially as an adaptive mechanism explaining why FR does not efficiently kill UM tumor cells or regress UM tumor xenografts. These results establish that oncogenic Gq/11 signaling is a crucial driver of metabolic reprogramming in UM and lay a foundation for studies aimed at targeting metabolic reprogramming for therapeutic development.
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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 Socratic graph.