ArticleProceedings of the National Academy of Sciences of the United States of America2022
MITF deficiency accelerates GNAQ-driven uveal melanoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- MITF maintains genome stability in nonmelanocyte lineages.Molecular oncology · 2026Article
- Modeling rare melanoma subtypes: mechanisms, microenvironments and translational opportunities.Frontiers in oncology · 2026Review
- Dualistic Role of MITF in Uveal Melanoma: Defining Two Distinct Cellular Subpopulations With Prognostic and Therapeutic Implications.Investigative ophthalmology & visual science · 2025Article
- Mitfa-Independent Melanocyte Progenitors are Highly Susceptible to GNAQ-induced Uveal Melanoma in Adult Zebrafish.bioRxiv : the preprint server for biology · 2025Article
- Super-enhancers orchestrate transcriptional dysregulation and metabolic reprogramming in uveal melanoma.Communications biology · 2025Article
- Death associated protein like 1 acts as a novel tumor suppressor in melanoma by increasing the stability of P21 protein.Molecular and cellular biochemistry · 2025Article
- Phenolic Glycoside Monomer fromCurrent medicinal chemistry · 2025Article
- Genetic Features of Uveal Melanoma.Genes · 2024Review
- Review
- EHMT2 promotes tumorigenesis inActa pharmaceutica Sinica. B · 2024Article
- Disrupting Hedgehog signaling in melanocytes by SUFU knockout leads to ocular melanocytosis and anterior segment malformation.Disease models & mechanisms · 2023Article
- Article
- Microphthalmia-Associated Transcription Factor: A Differentiation Marker in Uveal Melanoma.International journal of molecular sciences · 2023Article
- Piebaldism and chromatophore development in reptiles are linked to the tfec gene.Current biology : CB · 2023Article
- MITF deficiency and oncogenic GNAQ each promote proliferation programs in zebrafish melanocyte lineage cells.Pigment cell & melanoma research · 2022Article
- Evaluation of the Therapeutic Potential of Histone Deacetylase 6 Inhibitors for Primary and Metastatic Uveal Melanoma.International journal of molecular sciences · 2022Review
- MITF deficiency accelerates GNAQ-driven uveal melanoma.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cutaneous melanoma (CM) and uveal melanoma (UM) both originate from the melanocytic lineage but are primarily driven by distinct oncogenic drivers, BRAF/NRAS or GNAQ/GNA11, respectively. The melanocytic master transcriptional regulator, MITF, is essential for both CM development and maintenance, but its role in UM is largely unexplored. Here, we use zebrafish models to dissect the key UM oncogenic signaling events and establish the role of MITF in UM tumors. Using a melanocytic lineage expression system, we showed that patient-derived mutations of GNAQ (GNAQQ209L) or its upstream CYSLTR2 receptor (CYSLTR2L129Q) both drive UM when combined with a cooperating mutation, tp53M214K/M214K. The tumor-initiating potential of the major GNAQ/11 effector pathways, YAP, and phospholipase C-β (PLCβ)–ERK was also investigated in this system and thus showed that while activated YAP (YAPAA) induced UM with high potency, the patient-derived PLCβ4 mutation (PLCB4D630Y) very rarely yielded UM tumors in the tp53M214K/M214K context. Remarkably, mitfa deficiency was profoundly UM promoting, dramatically accelerating the onset and progression of tumors induced by Tg(mitfa:GNAQQ209L);tp53M214K/M214K or Tg(mitfa:CYSLTR2L129Q);tp53M214K/M214K. Moreover, mitfa loss was sufficient to cooperate with GNAQQ209L to drive tp53–wild type UM development and allowed Tg(mitfa:PLCB4D630Y);tp53M214K/M214K melanocyte lineage cells to readily form tumors. Notably, all of the mitfa−/− UM tumors, including those arising in Tg(mitfa:PLCB4D630Y);tp53M214K/M214K;mitfa−/− zebrafish, displayed nuclear YAP while lacking hyperactive ERK indicative of PLCβ signaling. Collectively, these data show that YAP signaling is the major mediator of UM and that MITF acts as a bona fide tumor suppressor in UM in direct opposition to its essential role in CM.
Indexed as
Identifiers
What OpenQuestion holds
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.