Evidence map›Paper›PMID 36670102›Full record

ArticleNature communications2023

Polycomb deficiency drives a FOXP2-high aggressive state targetable by epigenetic inhibitors.

Fan Chen, Aria L Byrd, Jinpeng Liu, Robert M Flight, Tanner J DuCote, Kassandra J Naughton, Xiulong Song, Abigail R Edgin, Alexsandr Lukyanchuk, Danielle T Dixon and 7 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

12 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Dual Effect ofBiology · 2026
    Article
  7. FOXP2/SOS1/AKT negative feedback loop inhibits cell proliferation in KRAS-mutant colorectal cancer.Apoptosis : an international journal on programmed cell death · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Using 3-Dimensional Cultures to Propagate Genetically Modified Lung Organoids.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  12. Using Artificial Intelligence to Identify Tumor Microenvironment Heterogeneity in Non-Small Cell Lung Cancers.Laboratory investigation; a journal of technical methods and pathology · 2023
    Article
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

17 authors at 3 institutions in 2 countries.

Fan ChenDepartment of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY, 40536, USA.
Aria L ByrdDepartment of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY, 40536, USA.
Jinpeng LiuDepartment of Internal Medicine, University of Kentucky, Lexington, KY, 40536, USA.
Robert M FlightDepartment of Molecular & Cellular Biochemistry, University of Kentucky, Lexington, KY, 40536, USA.ORCID 0000-0001-8141-7788
Tanner J DuCoteDepartment of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY, 40536, USA.
Kassandra J NaughtonDepartment of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY, 40536, USA.
Xiulong SongDepartment of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY, 40536, USA.
Abigail R EdginDepartment of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY, 40536, USA.ORCID 0000-0003-2702-5198
Alexsandr LukyanchukDepartment of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY, 40536, USA.
Danielle T DixonDepartment of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY, 40536, USA.
Christian M GosserDepartment of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY, 40536, USA.
Dave-Preston EsoeDepartment of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY, 40536, USA.
Rani D JayswalMarkey Cancer Center Biostatistics and Bioinformatics Shared Resource Facility, Lexington, KY, 40536, USA.
Stuart H OrkinDepartment of Hematology/Oncology, Boston Children's Hospital, Boston, MA, 02115, USA.ORCID 0000-0002-0313-152X
Hunter N B MoseleyDepartment of Molecular & Cellular Biochemistry, University of Kentucky, Lexington, KY, 40536, USA.
Chi WangDepartment of Internal Medicine, University of Kentucky, Lexington, KY, 40536, USA.
Christine Fillmore BrainsonDepartment of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY, 40536, USA. cfbrainson@uky.edu.ORCID 0000-0002-0854-5043
University of Kentucky · USBoston Children's Hospital · USMarkey Cancer Center · US

Funding

University of Kentucky Markey Cancer Center Support Grant ECIA SupplementP30CA177558 · NCI · UNIVERSITY OF KENTUCKY · PI Bernard Mark Evers · 2013 to 2026
$38.3M
University of Kentucky Center for Cancer MetabolismP20GM121327 · NIGMS · UNIVERSITY OF KENTUCKY · PI Jianhang Jia · 2017 to 2026
$25.0M
TRAINING GRANT IN MOLECULAR MECHANISMS OF TOXICITY.T32ES007266 · NIEHS · UNIVERSITY OF KENTUCKY · PI LIU, XIAOQI, MELLON, ISABEL W · 1990 to 2020
$3.7M
Targeting Epigenetic Heterogeneity to Improve Lung Cancer Immunotherapy ResponseR01CA237643 · NCI · UNIVERSITY OF KENTUCKY · PI BRAINSON, CHRISTINE FILLMORE · 2019 to 2023
$1.9M
Defining epigenetic vulnerabilities of subtype-specific lung cancersK22CA201036 · NCI · UNIVERSITY OF KENTUCKY · PI BRAINSON, CHRISTINE FILLMORE · 2016 to 2018
$482k
Bronchiolar Dysplasia in COPD is Governed by Loss of Polycomb Repressive Complex 2F31HL151111 · NHLBI · UNIVERSITY OF KENTUCKY · PI BYRD, ARIA · 2020 to 2021
$57k
NCI NIH HHS K22 CA201036NCI NIH HHS P30 CA177558NCI NIH HHS R01 CA237643NHLBI NIH HHS F31 HL151111NIEHS NIH HHS T32 ES007266NIGMS NIH HHS P20 GM121327
6 · The paper itself

Abstract

Inhibitors of the Polycomb Repressive Complex 2 (PRC2) histone methyltransferase EZH2 are approved for certain cancers, but realizing their wider utility relies upon understanding PRC2 biology in each cancer system. Using a genetic model to delete Ezh2 in KRAS-driven lung adenocarcinomas, we observed that Ezh2 haplo-insufficient tumors were less lethal and lower grade than Ezh2 fully-insufficient tumors, which were poorly differentiated and metastatic. Using three-dimensional cultures and in vivo experiments, we determined that EZH2-deficient tumors were vulnerable to H3K27 demethylase or BET inhibitors. PRC2 loss/inhibition led to de-repression of FOXP2, a transcription factor that promotes migration and stemness, and FOXP2 could be suppressed by BET inhibition. Poorly differentiated human lung cancers were enriched for an H3K27me3-low state, representing a subtype that may benefit from BET inhibition as a single therapy or combined with additional EZH2 inhibition. These data highlight diverse roles of PRC2 in KRAS-driven lung adenocarcinomas, and demonstrate the utility of three-dimensional cultures for exploring epigenetic drug sensitivities for cancer.

Indexed as

Adenocarcinoma of LungNeoplasmsEnhancer of Zeste Homolog 2 ProteinEpigenesis, GeneticForkhead Transcription FactorsHumansPolycomb-Group ProteinsPolycomb Repressive Complex 2Proto-Oncogene Proteins p21(ras)Enhancer of Zeste Homolog 2 ProteinForkhead Transcription FactorsFOXP2 protein, humanPolycomb-Group ProteinsPolycomb Repressive Complex 2Proto-Oncogene Proteins p21(ras)

Identifiers

PMID36670102
PMCPMC9859827
OpenAlexW4317581730

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.