Evidence map›Paper›PMID 31941995›Full record

ArticleScientific reports2020

Chronic IL-1β-induced inflammation regulates epithelial-to-mesenchymal transition memory phenotypes via epigenetic modifications in non-small cell lung cancer.

Rui Li, Stephanie L Ong, Linh M Tran, Zhe Jing, Bin Liu, Stacy J Park, Zi Ling Huang, Tonya C Walser, Eileen L Heinrich, Gina Lee and 8 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 71 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 1 pooled it
5.5field-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

71 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.

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  10. Correlations ofQuantitative imaging in medicine and surgery · 2026
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11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 1 institution in 1 country.

Rui LiPulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, 90025, California, USA.ORCID http://orcid.org/0000-0002-5620-4833
Stephanie L OngDepartment of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, 90025, California, USA.
Linh M TranPulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, 90025, California, USA.
Zhe JingPulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, 90025, California, USA.
Bin LiuPulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, 90025, California, USA.
Stacy J ParkPulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, 90025, California, USA.
Zi Ling HuangPulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, 90025, California, USA.
Tonya C WalserPulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, 90025, California, USA.
Eileen L HeinrichDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, 90025, California, USA.
Gina LeePulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, 90025, California, USA.
Ramin Salehi-RadPulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, 90025, California, USA.
William P CrossonDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, 90025, California, USA.
Paul C PaganoDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, 90025, California, USA.
Manash K PaulPulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, 90025, California, USA.
Shili XuDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, 90025, California, USA.
Harvey HerschmanDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, 90025, California, USA.
Kostyantyn KrysanPulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, 90025, California, USA.
Steven DubinettPulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, 90025, California, USA. sdubinett@mednet.ucla.edu.
University of California, Los Angeles · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
Integrated Molecular, Cellular, and Imaging Characterization of Screen-Detected Lung CancerU01CA196408 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ABERLE, DENISE R., DUBINETT, STEVEN M. · 2015 to 2021
$7.1M
The Boston University-UCLA Lung Cancer Biomarker Development LabU01CA214182 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI ABERLE, DENISE R., DUBINETT, STEVEN M. · 2016 to 2021
$3.1M
NCATS NIH HHS UL1 TR001881NCI NIH HHS P30 CA016042NCI NIH HHS U01 CA196408NCI NIH HHS U01 CA214182
6 · The paper itself

Abstract

Chronic inflammation facilitates tumor progression. We discovered that a subset of non-small cell lung cancer cells underwent a gradually progressing epithelial-to-mesenchymal (EMT) phenotype following a 21-day exposure to IL-1β, an abundant proinflammatory cytokine in the at-risk for lung cancer pulmonary and the lung tumor microenvironments. Pathway analysis of the gene expression profile and in vitro functional studies revealed that the EMT and EMT-associated phenotypes, including enhanced cell invasion, PD-L1 upregulation, and chemoresistance, were sustained in the absence of continuous IL-1β exposure. We referred to this phenomenon as EMT memory. Utilizing a doxycycline-controlled SLUG expression system, we found that high expression of the transcription factor SLUG was indispensable for the establishment of EMT memory. High SLUG expression in tumors of lung cancer patients was associated with poor survival. Chemical or genetic inhibition of SLUG upregulation prevented EMT following the acute IL-1β exposure but did not reverse EMT memory. Chromatin immunoprecipitation and methylation-specific PCR further revealed a SLUG-mediated temporal regulation of epigenetic modifications, including accumulation of H3K27, H3K9, and DNA methylation, in the CDH1 (E-cadherin) promoter following the chronic IL-1β exposure. Chemical inhibition of DNA methylation not only restored E-cadherin expression in EMT memory, but also primed cells for chemotherapy-induced apoptosis.

Indexed as

Epigenesis, GeneticEpithelial-Mesenchymal TransitionAntigens, CDCadherinsCarcinoma, Non-Small-Cell LungDNA MethylationGene Expression Regulation, NeoplasticHumansImmunologic MemoryInflammationInterleukin-1betaLung NeoplasmsPhenotypeTumor Cells, CulturedAntigens, CDCadherinsCDH1 protein, humanIL1B protein, humanInterleukin-1beta

Identifiers

PMID31941995
PMCPMC6962381
OpenAlexW3000456443

What OpenQuestion holds

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LicenceCC BY
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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.