Evidence map›Paper›PMID 30612740›Full record

ArticleCell2019

METTL13 Methylation of eEF1A Increases Translational Output to Promote Tumorigenesis.

Shuo Liu, Simone Hausmann, Scott Moore Carlson, Mary Esmeralda Fuentes, Joel William Francis, Renjitha Pillai, Shane Michael Lofgren, Laura Hulea, Kristofferson Tandoc, Jiuwei Lu and 15 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
120citing papers in PubMed, 1 pooled it
9.1field-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

120 citing papers in PubMed, 1 synthesis or guideline pooled it, 201 citations in OpenAlex.

  1. Pooled it
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  14. METTL10-Mediated PIAS3 Methylation Links Purine Metabolism to Gastric Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
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60 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

25 authors at 5 institutions in 2 countries.

Shuo LiuDepartment of Biology, Stanford University, Stanford, CA 94305, USA.
Simone HausmannDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Scott Moore CarlsonDepartment of Biology, Stanford University, Stanford, CA 94305, USA.
Mary Esmeralda FuentesDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Joel William FrancisDepartment of Biology, Stanford University, Stanford, CA 94305, USA.
Renjitha PillaiDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Shane Michael LofgrenDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Laura HuleaLady Davis Institute and Gerald Bronfman Department of Oncology, McGill University, Montreal, QC H3T 1E2, Canada.
Kristofferson TandocLady Davis Institute and Gerald Bronfman Department of Oncology, McGill University, Montreal, QC H3T 1E2, Canada.
Jiuwei LuDepartment of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA.
Ami LiDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Nicholas Dang NguyenDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Marcello CaporicciDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Michael Paul KimDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Anirban MaitraDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Huamin WangDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Ignacio Ivan WistubaDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
John Anthony PorcoDepartment of Chemistry, Boston University, Boston, MA 02215, USA.
Michael Cory BassikDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Joshua Eric EliasDeparment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jikui SongDepartment of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA.
Ivan TopisirovicLady Davis Institute and Gerald Bronfman Department of Oncology, McGill University, Montreal, QC H3T 1E2, Canada.
Capucine Van RechemDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Pawel Karol MazurDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: pkmazur@mdanderson.org.
Or GozaniDepartment of Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: ogozani@stanford.edu.
The University of Texas MD Anderson Cancer Center · USStanford University · USMcGill University · CAUniversity of California, Riverside · USBoston University · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
UNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI GIBBONS, DON LYNN · 1996 to 2024
$57.4M
Supplement to Enhance Wellness and Resiliency in the Graduate EnvironmentT32GM007276 · NIGMS · STANFORD UNIVERSITY · PI MORRISON, ASHBY J. · 1985 to 2023
$32.9M
Chemical Synthesis of Complex Natural Products for Translational ScienceR35GM118173 · NIGMS · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI JOHN A. PORCO · 2016 to 2026
$8.2M
Mechanistic Insights into Mammalian DNA MethylationR35GM119721 · NIGMS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI Jikui Song · 2016 to 2026
$5.3M
Function of PHD Domain Proteins in Chromatin RegulationR01GM079641 · NIGMS · STANFORD UNIVERSITY · PI GOZANI, OR P. · 2007 to 2020
$4.5M
Accelerating drug development and repurposing using systematic genetic interactioDP2HD084069 · NICHD · STANFORD UNIVERSITY · PI BASSIK, MICHAEL C · 2014 to 2014
$2.4M
Control of Protein Synthesis by the UPS Under StressR01CA202021 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI RONAI, ZEEV A. · 2016 to 2020
$2.3M
Defining diverse roles of p53 in pancreatic cancerK08CA218690 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KIM, MICHAEL PAUL · 2017 to 2021
$853k
The SMYD3-ERK5 signaling module in pancreatic cancerR00CA197816 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MAZUR, PAWEL K. · 2017 to 2019
$732k
The role of PRDM1 in epigenetic regulation and tumor suppressionK99CA190803 · NCI · STANFORD UNIVERSITY · PI CARLSON, SCOTT MOORE · 2015 to 2016
$225k
NCI NIH HHS K08 CA218690NCI NIH HHS K99 CA190803NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA070907NCI NIH HHS R00 CA197816NCI NIH HHS R01 CA202021NICHD NIH HHS DP2 HD084069NIGMS NIH HHS R01 GM079641NIGMS NIH HHS R35 GM118173NIGMS NIH HHS R35 GM119721NIGMS NIH HHS T32 GM007276
6 · The paper itself

Abstract

Increased protein synthesis plays an etiologic role in diverse cancers. Here, we demonstrate that METTL13 (methyltransferase-like 13) dimethylation of eEF1A (eukaryotic elongation factor 1A) lysine 55 (eEF1AK55me2) is utilized by Ras-driven cancers to increase translational output and promote tumorigenesis in vivo. METTL13-catalyzed eEF1A methylation increases eEF1A's intrinsic GTPase activity in vitro and protein production in cells. METTL13 and eEF1AK55me2 levels are upregulated in cancer and negatively correlate with pancreatic and lung cancer patient survival. METTL13 deletion and eEF1AK55me2 loss dramatically reduce Ras-driven neoplastic growth in mouse models and in patient-derived xenografts (PDXs) from primary pancreatic and lung tumors. Finally, METTL13 depletion renders PDX tumors hypersensitive to drugs that target growth-signaling pathways. Together, our work uncovers a mechanism by which lethal cancers become dependent on the METTL13-eEF1AK55me2 axis to meet their elevated protein synthesis requirement and suggests that METTL13 inhibition may constitute a targetable vulnerability of tumors driven by aberrant Ras signaling.

Indexed as

AdultAgedAnimalsCarcinogenesisCell LineCell Transformation, NeoplasticFemaleHEK293 CellsHeterograftsHumansLysineMaleMethylationMethyltransferasesMiceMice, Inbred C57BLEEF1A1 protein, humanEEF1AKNMT protein, humanLysineMethyltransferasesPeptide Elongation Factor 1eEF1Alung cancerlysine methylationMETTL13pancreatic cancerprotein methylationRAStranslationtranslation elongation

Identifiers

PMID30612740
PMCPMC6499081
OpenAlexW2907984739

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.