Evidence map›Paper›PMID 31784510›Full record

ArticleNature communications2019

A high-throughput screen identifies that CDK7 activates glucose consumption in lung cancer cells.

Chiara Ghezzi, Alicia Wong, Bao Ying Chen, Bernard Ribalet, Robert Damoiseaux, Peter M Clark

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.3field-weighted citation impact, top 23% 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

22 citing papers in PubMed, 64 citations in OpenAlex.

  1. Review
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  7. Review
  8. Structural basis of Cdk7 activation by dual T-loop phosphorylation.bioRxiv : the preprint server for biology · 2024
    Article
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  17. Review
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  19. Article
  20. MUC16 promotes EOC proliferation by regulating GLUT1 expression.Journal of cellular and molecular medicine · 2021
    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

6 authors at 2 institutions in 1 country.

Chiara GhezziCrump Institute for Molecular Imaging, University of California, Los Angeles, CA, 90095, USA.
Alicia WongCrump Institute for Molecular Imaging, University of California, Los Angeles, CA, 90095, USA.
Bao Ying ChenCrump Institute for Molecular Imaging, University of California, Los Angeles, CA, 90095, USA.
Bernard RibaletDepartment of Physiology, University of California, Los Angeles, CA, 90095, USA.
Robert DamoiseauxCrump Institute for Molecular Imaging, University of California, Los Angeles, CA, 90095, USA.
Peter M ClarkCrump Institute for Molecular Imaging, University of California, Los Angeles, CA, 90095, USA. pclark@mednet.ucla.edu.ORCID http://orcid.org/0000-0002-0786-9054
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
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
NCATS NIH HHS UL1 TR000124NCI NIH HHS P30 CA016042
6 · The paper itself

Abstract

Elevated glucose consumption is fundamental to cancer, but selectively targeting this pathway is challenging. We develop a high-throughput assay for measuring glucose consumption and use it to screen non-small-cell lung cancer cell lines against bioactive small molecules. We identify Milciclib that blocks glucose consumption in H460 and H1975, but not in HCC827 or A549 cells, by decreasing SLC2A1 (GLUT1) mRNA and protein levels and by inhibiting glucose transport. Milciclib blocks glucose consumption by targeting cyclin-dependent kinase 7 (CDK7) similar to other CDK7 inhibitors including THZ1 and LDC4297. Enhanced PIK3CA signaling leads to CDK7 phosphorylation, which promotes RNA Polymerase II phosphorylation and transcription. Milciclib, THZ1, and LDC4297 lead to a reduction in RNA Polymerase II phosphorylation on the SLC2A1 promoter. These data indicate that our high-throughput assay can identify compounds that regulate glucose consumption and that CDK7 is a key regulator of glucose consumption in cells with an activated PI3K pathway.

Indexed as

A549 CellsCarcinoma, Non-Small-Cell LungCell Line, TumorClass I Phosphatidylinositol 3-KinasesCyclin-Dependent Kinase-Activating KinaseCyclin-Dependent KinasesGlucoseGlucose Transporter Type 1High-Throughput Screening AssaysHumansLung NeoplasmsPhenylenediaminesPhosphorylationProtein Kinase InhibitorsPyrazolesPyrimidinesCDK7 protein, humanClass I Phosphatidylinositol 3-KinasesCyclin-Dependent Kinase-Activating KinaseCyclin-Dependent KinasesGlucoseGlucose Transporter Type 1LDC4297N,1,4,4-tetramethyl-8-((4-(4-methylpiperazin-1-yl)phenyl)amino)-4,5-dihydro-1H-pyrazolo(4,3-h)quinazoline-3-carboxamidePhenylenediaminesPIK3CA protein, humanProtein Kinase InhibitorsPyrazolesPyrimidinesQuinazolinesRNA, MessengerRNA Polymerase IITHZ1 compoundTriazines

Identifiers

PMID31784510
PMCPMC6884612
OpenAlexW2990959882

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.