Evidence map›Paper›PMID 39117659›Full record

ArticleNature communications2024

Histone-methyltransferase KMT2D deficiency impairs the Fanconi anemia/BRCA pathway upon glycolytic inhibition in squamous cell carcinoma.

Wei Liu, Hongchao Cao, Jing Wang, Areeg Elmusrati, Bing Han, Wei Chen, Ping Zhou, Xiyao Li, Stephen Keysar, Antonio Jimeno and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
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

10 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
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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

11 authors.

Wei Liu *Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0001-6435-6696
Hongchao Cao *Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
Jing WangJonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
Areeg ElmusratiJonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
Bing HanJonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
Wei ChenJonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
Ping ZhouJonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
Xiyao LiJonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
Stephen KeysarDivision of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Antonio JimenoDivision of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Cun-Yu WangJonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA. cwang@dentistry.ucla.edu.ORCID 0000-0002-3885-5149

Funding

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 R01 CA236878NIDCR NIH HHS R01 DE029173NIDCR NIH HHS R01 DE030445U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA236878U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR) R01DE029173U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR) R01DE030445
6 · The paper itself

Abstract

Histone lysine methyltransferase 2D (KMT2D) is the most frequently mutated epigenetic modifier in head and neck squamous cell carcinoma (HNSCC). However, the role of KMT2D in HNSCC tumorigenesis and whether its mutations confer any therapeutic vulnerabilities remain unknown. Here we show that KMT2D deficiency promotes HNSCC growth through increasing glycolysis. Additionally, KMT2D loss decreases the expression of Fanconi Anemia (FA)/BRCA pathway genes under glycolytic inhibition. Mechanistically, glycolytic inhibition facilitates the occupancy of KMT2D to the promoter/enhancer regions of FA genes. KMT2D loss reprograms the epigenomic landscapes of FA genes by transiting their promoter/enhancer states from active to inactive under glycolytic inhibition. Therefore, combining the glycolysis inhibitor 2-DG with DNA crosslinking agents or poly (ADP-ribose) polymerase (PARP) inhibitors preferentially inhibits tumor growth of KMT2D-deficient mouse HNSCC and patient-derived xenografts (PDXs) harboring KMT2D-inactivating mutations. These findings provide an epigenomic basis for developing targeted therapies for HNSCC patients with KMT2D-inactivating mutations.

Indexed as

GlycolysisSquamous Cell Carcinoma of Head and NeckAnimalsBRCA1 ProteinBRCA2 ProteinCell Line, TumorDNA-Binding ProteinsFanconi AnemiaFemaleGene Expression Regulation, NeoplasticHead and Neck NeoplasmsHistone-Lysine N-MethyltransferaseHumansMiceMyeloid-Lymphoid Leukemia ProteinNeoplasm ProteinsBRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinBRCA2 protein, humanDNA-Binding ProteinsHistone-Lysine N-MethyltransferaseKMT2D protein, humanKmt2d protein, mouseMyeloid-Lymphoid Leukemia ProteinNeoplasm ProteinsPoly(ADP-ribose) Polymerase Inhibitors

Identifiers

PMID39117659
PMCPMC11310337

What OpenQuestion holds

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Registered trials

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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.