Evidence map›Paper›PMID 31712311›Full record

ArticleThe Journal of biological chemistry2019

mTORC2 links growth factor signaling with epigenetic regulation of iron metabolism in glioblastoma.

Kenta Masui, Mio Harachi, Shiro Ikegami, Huijun Yang, Hiromi Onizuka, William H Yong, Timothy F Cloughesy, Yoshihiro Muragaki, Takakazu Kawamata, Nobutaka Arai and 4 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

22 citing papers in PubMed, 37 citations in OpenAlex.

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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

14 authors at 5 institutions in 2 countries.

Kenta MasuiDepartment of Pathology, Tokyo Women's Medical University, Shinjuku, Tokyo 162-8666, Japan masui-kn@twmu.ac.jp.
Mio HarachiDepartment of Pathology, Tokyo Women's Medical University, Shinjuku, Tokyo 162-8666, Japan.ORCID 0000-0002-5824-6690
Shiro IkegamiLudwig Institute for Cancer Research, University of California San Diego, La Jolla, California 92093.
Huijun YangLudwig Institute for Cancer Research, University of California San Diego, La Jolla, California 92093.
Hiromi OnizukaDepartment of Pathology, Tokyo Women's Medical University, Shinjuku, Tokyo 162-8666, Japan.
William H YongHenry Singleton Brain Tumor Program, David Geffen UCLA School of Medicine, Los Angeles, California 90095.
Timothy F CloughesyHenry Singleton Brain Tumor Program, David Geffen UCLA School of Medicine, Los Angeles, California 90095.
Yoshihiro MuragakiDepartment of Neurosurgery, Tokyo Women's Medical University, Shinjuku, Tokyo 162-8666, Japan.
Takakazu KawamataDepartment of Neurosurgery, Tokyo Women's Medical University, Shinjuku, Tokyo 162-8666, Japan.
Nobutaka AraiLaboratory of Neuropathology, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan.
Takashi KomoriDepartment of Neuropathology, Tokyo Metropolitan Neurological Hospital, Musashinodai, Tokyo 183-0042, Japan.ORCID 0000-0002-6812-2149
Webster K CaveneeLudwig Institute for Cancer Research, University of California San Diego, La Jolla, California 92093.
Paul S MischelLudwig Institute for Cancer Research, University of California San Diego, La Jolla, California 92093.
Noriyuki ShibataDepartment of Pathology, Tokyo Women's Medical University, Shinjuku, Tokyo 162-8666, Japan.
Tokyo Women's Medical University · JPUniversity of California San Diego · USUniversity of California, Los Angeles · USTokyo Metropolitan Institute of Medical Science · JPTokyo Metropolitan Neurological Hospital · JP

Funding

UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI David A. Nathanson · 2017 to 2026
$25.2M
QUANTITATIVE IMAGE ANALYSIS SPECIALIZED RESOURCE COREU54CA119347 · NCI · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI SAWYERS, CHARLES L · 2005 to 2009
$17.8M
The role of mTORC2 in reprogramming cancer cell metabolismR01NS073831 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MISCHEL, PAUL S · 2011 to 2020
$3.4M
NCI NIH HHS P50 CA211015NCI NIH HHS U54 CA119347NINDS NIH HHS R01 NS073831
6 · The paper itself

Abstract

In cancer, aberrant growth factor receptor signaling reprograms cellular metabolism and global gene transcription to drive aggressive growth, but the underlying mechanisms are not well-understood. Here we show that in the highly lethal brain tumor glioblastoma (GBM), mTOR complex 2 (mTORC2), a critical core component of the growth factor signaling system, couples acetyl-CoA production with nuclear translocation of histone-modifying enzymes including pyruvate dehydrogenase and class IIa histone deacetylases to globally alter histone acetylation. Integrated analyses in orthotopic mouse models and in clinical GBM samples reveal that mTORC2 controls iron metabolisms via histone H3 acetylation of the iron-related gene promoter, promoting tumor cell survival. These results nominate mTORC2 as a critical epigenetic regulator of iron metabolism in cancer.

Indexed as

Epigenesis, GeneticActive Transport, Cell NucleusAnimalsBrain NeoplasmsCell Line, TumorCell SurvivalGene Expression Regulation, NeoplasticGlioblastomaHistonesHumansImmediate-Early ProteinsIntercellular Signaling Peptides and ProteinsIronMechanistic Target of Rapamycin Complex 2MetabolomeMiceAKT1 protein, humanHistonesImmediate-Early ProteinsIntercellular Signaling Peptides and ProteinsIronMechanistic Target of Rapamycin Complex 2Protein Serine-Threonine KinasesProto-Oncogene Proteins c-aktPyruvate Dehydrogenase (Lipoamide)Serum-Glucocorticoid Regulated Kinasesacetyl coenzyme A (acetyl-CoA)glioblastomaglucose metabolismhistone acetylationiron metabolismmammalian target of rapamycin (mTOR)

Identifiers

PMID31712311
PMCPMC6926466
OpenAlexW2986482640

What OpenQuestion holds

Textmetadata
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.