Evidence map›Paper›PMID 28486107›Full record

ArticleCancer cell2017

RasGRP3 Mediates MAPK Pathway Activation in GNAQ Mutant Uveal Melanoma.

Xu Chen, Qiuxia Wu, Philippe Depeille, Peirong Chen, Sophie Thornton, Helen Kalirai, Sarah E Coupland, Jeroen P Roose, Boris C Bastian

Open access · bronzeAbstract read
In one paragraph

Article in Cancer cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed, 1 pooled it
11.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

110 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 citations in OpenAlex.

  1. Guideline
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  5. Oncogenic Gα signaling requires AP-3-dependent recruitment to the endolysosomal compartment.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  19. Article
  20. Management of liver metastases from uveal melanoma.The British journal of surgery · 2025
    Review

50 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Xu ChenDepartments of Dermatology and Pathology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: xu.chen@ucsf.edu.
Qiuxia WuDepartments of Dermatology and Pathology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Philippe DepeilleDepartment of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
Peirong ChenDepartments of Dermatology and Pathology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Sophie ThorntonDepartment of Molecular and Clinical Cancer Medicine, Institute of Translational Mewdicine, University of Liverpool, Liverpool L7 8TX, UK.
Helen KaliraiDepartment of Molecular and Clinical Cancer Medicine, Institute of Translational Mewdicine, University of Liverpool, Liverpool L7 8TX, UK.
Sarah E CouplandDepartment of Molecular and Clinical Cancer Medicine, Institute of Translational Mewdicine, University of Liverpool, Liverpool L7 8TX, UK.
Jeroen P RooseDepartment of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
Boris C BastianDepartments of Dermatology and Pathology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: boris.bastian@ucsf.edu.
University of California, San Francisco · USUniversity of Liverpool · GBUCSF Helen Diller Family Comprehensive Cancer Center · US

Funding

Understand the metabolic fitness of naïve T cellsP01AI091580 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JEROEN ROOSE · 2011 to 2026
$31.1M
TRANS-NETWORK PROJECTSU54CA143874 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI VAN OUDENAARDEN, ALEXANDER · 2009 to 2013
$15.1M
The GNAQ pathway as a therapeutic target in uveal melanomaR01CA142873 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BASTIAN, BORIS C. · 2010 to 2017
$2.2M
NCI NIH HHS R01 CA142873NCI NIH HHS U54 CA143874NIAID NIH HHS P01 AI091580
6 · The paper itself

Abstract

Constitutive activation of Gαq signaling by mutations in GNAQ or GNA11 occurs in over 80% of uveal melanomas (UMs) and activates MAPK. Protein kinase C (PKC) has been implicated as a link, but the mechanistic details remained unclear. We identified PKC δ and ɛ as required and sufficient to activate MAPK in GNAQ mutant melanomas. MAPK activation depends on Ras and is caused by RasGRP3, which is significantly and selectively overexpressed in response to GNAQ/11 mutation in UM. RasGRP3 activation occurs via PKC δ- and ɛ-dependent phosphorylation and PKC-independent, DAG-mediated membrane recruitment, possibly explaining the limited effect of PKC inhibitors to durably suppress MAPK in UM. The findings nominate RasGRP3 as a therapeutic target for cancers driven by oncogenic GNAQ/11.

Indexed as

MAP Kinase Signaling SystemMutationAnimalsCell Line, TumorCell ProliferationDiglyceridesEnzyme ActivationExtracellular Signal-Regulated MAP KinasesGTP-Binding Protein alpha SubunitsGTP-Binding Protein alpha Subunits, Gq-G11Guanine Nucleotide Exchange FactorsHumansMelanomaMice, NudePhosphorylationProtein Kinase C-deltaDiglyceridesExtracellular Signal-Regulated MAP KinasesGNA11 protein, humanGNAQ protein, humanGTP-Binding Protein alpha SubunitsGTP-Binding Protein alpha Subunits, Gq-G11Guanine Nucleotide Exchange FactorsPRKCD protein, humanPRKCE protein, humanProtein Kinase C-deltaProtein Kinase C-epsilonProtein Kinase InhibitorsRASGRP3 protein, humanras Guanine Nucleotide Exchange FactorsDAGGNA11GNAQMAPKmelanomaPKCRasGEFRasGRP3uveal melanoma

Identifiers

PMID28486107
PMCPMC5499527
OpenAlexW2613209365

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.