Evidence map›Paper›PMID 36778362›Full record

ArticlebioRxiv : the preprint server for biology2023

Glucose deprivation promotes pseudo-hypoxia and de-differentiation in lung adenocarcinoma.

Pasquale Saggese, Aparamita Pandey, Eileen Fung, Abbie Hall, Jane Yanagawa, Erika F Rodriguez, Tristan R Grogan, Giorgio Giurato, Giovanni Nassa, Annamaria Salvati and 3 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed, 5 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 2 countries.

Pasquale SaggeseDivision of Pulmonary Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Aparamita PandeyDivision of Pulmonary Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Eileen FungDivision of Pulmonary Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Abbie HallDivision of Pulmonary Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Jane YanagawaDivision of Thoracic Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Erika F RodriguezDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Tristan R GroganDivision of General Internal Medicine and Health Services Research, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Giorgio GiuratoLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry 'Scuola Medica Salernitana', University of Salerno, Baronissi (SA), Italy.
Giovanni NassaLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry 'Scuola Medica Salernitana', University of Salerno, Baronissi (SA), Italy.
Annamaria SalvatiLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry 'Scuola Medica Salernitana', University of Salerno, Baronissi (SA), Italy.
Alessandro WeiszLaboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry 'Scuola Medica Salernitana', University of Salerno, Baronissi (SA), Italy.
Steven M DubinettDivision of Pulmonary Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Claudio ScafoglioDivision of Pulmonary Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
University of California, Los Angeles · USUniversity of Salerno · IT

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Robert Damoiseaux · 1985 to 2026
$134.5M
Investigating the heterogeneity of glucose transport in lung adenocarcinomaR01CA237401 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SCAFOGLIO, CLAUDIO · 2020 to 2025
$3.1M
NCI NIH HHS P30 CA016042NCI NIH HHS R01 CA237401
6 · The paper itself

Abstract

Increased utilization of glucose is a hallmark of cancer. Several studies are investigating the efficacy of glucose restriction by glucose transporter blockade or glycolysis inhibition. However, the adaptations of cancer cells to glucose restriction are unknown. Here, we report the discovery that glucose restriction in lung adenocarcinoma (LUAD) induces cancer cell de-differentiation, leading to a more aggressive phenotype. Glucose deprivation causes a reduction in alpha-ketoglutarate (αKG), leading to attenuated activity of αKG-dependent histone demethylases and histone hypermethylation. We further show that this de-differentiated phenotype depends on unbalanced EZH2 activity, causing inhibition of prolyl-hydroxylase PHD3 and increased expression of hypoxia inducible factor 1α (HIF1α), triggering epithelial to mesenchymal transition. Finally, we identified an HIF1α-dependent transcriptional signature with prognostic significance in human LUAD. Our studies further current knowledge of the relationship between glucose metabolism and cell differentiation in cancer, characterizing the epigenetic adaptation of cancer cells to glucose deprivation and identifying novel targets to prevent the development of resistance to therapies targeting glucose metabolism.

Indexed as

EpigeneticsEZH2GlucoseHIF1aLung cancer

Identifiers

PMID36778362
PMCPMC9915520
OpenAlexW4318764014

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.