Evidence map›Paper›PMID 33743195›Full record

ArticleMolecular cell2021

Targeting KDM4A epigenetically activates tumor-cell-intrinsic immunity by inducing DNA replication stress.

Wuchang Zhang, Wei Liu, Lingfei Jia, Demeng Chen, Insoon Chang, Michael Lake, Laurent A Bentolila, Cun-Yu Wang

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

Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 1 pooled it
5.6field-weighted citation impact, top 3% 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

58 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 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

8 authors at 2 institutions in 1 country.

Wuchang ZhangJonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Wei LiuJonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Lingfei JiaJonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Demeng ChenJonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Insoon ChangJonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Michael LakeAdvanced Light Microscopy and Spectroscopy Laboratory, California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Laurent A BentolilaAdvanced Light Microscopy and Spectroscopy Laboratory, California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cun-Yu WangJonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: cwang@dentistry.ucla.edu.
University of California, Los Angeles · USCalifornia NanoSystems Institute · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Molecular and Genetic Determinants of Invasion in HNSCCR01DE015964 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WANG, CUN-YU · 2004 to 2019
$6.6M
Molecular and Epigenetic Control of Wnt/b-catenin-mediated oncogenesis by KDM4BR01CA236878 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WANG, CUN-YU · 2020 to 2024
$2.1M
Targeting Super-Enhancers Suppresses Cancer Stemness and Invasion of HNSCCR01DE029173 · NIDCR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WANG, CUN-YU · 2020 to 2024
$2.0M
The Inhibition of HNSCC Growth and Metastasis by Targeting KDM4AR01DE030445 · NIDCR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WANG, CUN-YU · 2021 to 2024
$1.6M
NCI NIH HHS P30 CA016042NCI NIH HHS R01 CA236878NIDCR NIH HHS R01 DE015964NIDCR NIH HHS R01 DE029173NIDCR NIH HHS R01 DE030445
6 · The paper itself

Abstract

Developing strategies to activate tumor-cell-intrinsic immune response is critical for improving tumor immunotherapy by exploiting tumor vulnerability. KDM4A, as a histone H3 lysine 9 trimethylation (H3K9me3) demethylase, has been found to play a critical role in squamous cell carcinoma (SCC) growth and metastasis. Here we report that KDM4A inhibition promoted heterochromatin compaction and induced DNA replication stress, which elicited antitumor immunity in SCC. Mechanistically, KDM4A inhibition promoted the formation of liquid-like HP1γ puncta on heterochromatin and stall DNA replication, which activated tumor-cell-intrinsic cGAS-STING signaling through replication-stress-induced cytosolic DNA accumulation. Moreover, KDM4A inhibition collaborated with PD1 blockade to inhibit SCC growth and metastasis by recruiting and activating CD8

Indexed as

Epigenesis, GeneticAnimalsCarcinoma, Squamous CellCD8-Positive T-LymphocytesCell Line, TumorChemokinesChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneDNA DamageDNA ReplicationEpithelial CellsGene DeletionHistone DemethylasesHumansImmunityJumonji Domain-Containing Histone DemethylasesChemokinesChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneHistone DemethylasesJMJD2A protein, mouseJumonji Domain-Containing Histone DemethylasesKDM4A protein, humanProgrammed Cell Death 1 ReceptorReceptors, CXCR3cancer stem cellsDNA replication stressH3K9me3head and neck squamous cell carcinomaheterochromatin condensatesimmune surveillanceKDM4AmetastasisPD-1 blockadePhase separation

Identifiers

PMID33743195
PMCPMC8141018
OpenAlexW3137617968

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.