Evidence map›Paper›PMID 33147463›Full record

ArticleCell reports2020

G9a Promotes Breast Cancer Recurrence through Repression of a Pro-inflammatory Program.

Nathaniel W Mabe, Nina Marie G Garcia, Shayna E Wolery, Rachel Newcomb, Ryan C Meingasner, Brittany A Vilona, Ryan Lupo, Chao-Chieh Lin, Jen-Tsan Chi, James V Alvarez

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

24 citing papers in PubMed, 38 citations in OpenAlex.

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  11. Frontiers in genetics · 2024
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  19. RIPK3 signaling and its role in the pathogenesis of cancers.Cellular and molecular life sciences : CMLS · 2021
    Review
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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

10 authors at 1 institution in 1 country.

Nathaniel W MabeDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.
Nina Marie G GarciaDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.
Shayna E WoleryDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.
Rachel NewcombDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.
Ryan C MeingasnerDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.
Brittany A VilonaDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.
Ryan LupoDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.
Chao-Chieh LinDepartment of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA; Center for Genomic and Computational Biology, Duke University, Durham, NC 27710, USA.
Jen-Tsan ChiDepartment of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA; Center for Genomic and Computational Biology, Duke University, Durham, NC 27710, USA.
James V AlvarezDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA. Electronic address: james.alvarez@duke.edu.
Duke University · US

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI JOHN N. NORTON · 1985 to 2026
$174.8M
Par-4 Regulation and Function in Breast Cancer Dormancy and RecurrenceR01CA208042 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ALVAREZ, JAMES V · 2016 to 2020
$2.1M
Exploring the role of polyploidy in tumor progressionF31CA239421 · NCI · DUKE UNIVERSITY · PI NEWCOMB, RACHEL LEANNE · 2019 to 2021
$103k
The Role of Epigenetic Plasticity in Breast Cancer RecurrenceF31CA220851 · NCI · DUKE UNIVERSITY · PI MABE, NATHANIEL · 2018 to 2019
$47k
NCI NIH HHS F31 CA220851NCI NIH HHS F31 CA239421NCI NIH HHS P30 CA014236NCI NIH HHS R01 CA208042
6 · The paper itself

Abstract

Dysregulated gene expression is a common feature of cancer and may underlie some aspects of tumor progression, including tumor relapse. Here, we show that recurrent mammary tumors exhibit global changes in gene expression and histone modifications and acquire dependence on the G9a histone methyltransferase. Genetic ablation of G9a delays tumor recurrence, and pharmacologic inhibition of G9a slows the growth of recurrent tumors. Mechanistically, G9a activity is required to silence pro-inflammatory cytokines, including tumor necrosis factor (TNF), through H3K9 methylation at gene promoters. G9a inhibition induces re-expression of these cytokines, leading to p53 activation and necroptosis. Recurrent tumors upregulate receptor interacting protein kinase-3 (RIPK3) expression and are dependent upon RIPK3 activity. High RIPK3 expression renders recurrent tumors sensitive to necroptosis following G9a inhibition. These findings demonstrate that G9a-mediated silencing of pro-necroptotic proteins is a critical step in tumor recurrence and suggest that G9a is a targetable dependency in recurrent breast cancer.

Indexed as

AnimalsCell DeathCell SurvivalEpigenesis, GeneticFemaleGene Expression Regulation, NeoplasticGene SilencingHistone-Lysine N-MethyltransferaseInflammationMammary Neoplasms, AnimalMice, NudeNecroptosisNeoplasm Recurrence, LocalReceptor-Interacting Protein Serine-Threonine KinasesRisk FactorsTranscription, GeneticG9a protein, mouseHistone-Lysine N-MethyltransferaseReceptor-Interacting Protein Serine-Threonine KinasesRIPK3 protein, humanTumor Necrosis Factor-alphaTumor Suppressor Protein p53breast cancercollateral sensitivityepigeneticsG9anecroptosisrecurrenceRIPK3

Identifiers

PMID33147463
PMCPMC7656293
OpenAlexW3095831264

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.