Evidence map›Paper›PMID 31372790›Full record

ArticleBreast cancer research and treatment2019

PK-M2-mediated metabolic changes in breast cancer cells induced by ionizing radiation.

Le Zhang, Justine Bailleul, Taha Yazal, Kevin Dong, David Sung, Amy Dao, Laura Gosa, David Nathanson, Kruttika Bhat, Sara Duhachek-Muggy and 4 more

Open access · greenAbstract read
In one paragraph

Article in Breast cancer research and treatment, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
0.6field-weighted citation impact, top 38% 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

18 citing papers in PubMed, 24 citations in OpenAlex.

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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

14 authors at 1 institution in 1 country.

Le ZhangDepartment of Radiation Oncology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA, 90095-1714, USA.
Justine BailleulDepartment of Radiation Oncology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA, 90095-1714, USA.
Taha YazalDepartment of Radiation Oncology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA, 90095-1714, USA.
Kevin DongDepartment of Radiation Oncology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA, 90095-1714, USA.
David SungDepartment of Radiation Oncology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA, 90095-1714, USA.
Amy DaoDepartment of Radiation Oncology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA, 90095-1714, USA.
Laura GosaDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
David NathansonDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Kruttika BhatDepartment of Radiation Oncology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA, 90095-1714, USA.
Sara Duhachek-MuggyDepartment of Radiation Oncology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA, 90095-1714, USA.
Claudia AlliDepartment of Radiation Oncology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA, 90095-1714, USA.
Milana Bochkur DratverDepartment of Radiation Oncology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA, 90095-1714, USA.
Frank PajonkDepartment of Radiation Oncology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA, 90095-1714, USA.
Erina VlashiDepartment of Radiation Oncology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA, 90095-1714, USA. evlashi@mednet.ucla.edu.ORCID http://orcid.org/0000-0002-2505-3577
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 SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI David A. Nathanson · 2017 to 2026
$25.2M
Glioblastoma, Glioblastoma Stem Cells and RadiotherapyR01CA200234 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PAJONK, FRANK · 2016 to 2020
$1.8M
Erythropoietin and Breast Cancer Stem CellsR01CA161294 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PAJONK, FRANK · 2012 to 2016
$1.6M
The 26S Proteasome in Cancer Stem CellsR01CA137110 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PAJONK, FRANK · 2009 to 2013
$1.6M
NCI NIH HHS P30 CA016042NCI NIH HHS P50 CA211015NCI NIH HHS R01 CA137110NCI NIH HHS R01 CA161294NCI NIH HHS R01 CA200234
6 · The paper itself

Abstract

purposeRadiotherapy (RT) constitutes an important part of breast cancer treatment. However, triple negative breast cancers (TNBC) exhibit remarkable resistance to most therapies, including RT. Developing new ways to radiosensitize TNBC cells could result in improved patient outcomes. The M2 isoform of pyruvate kinase (PK-M2) is believed to be responsible for the re-wiring of cancer cell metabolism after oxidative stress. The aim of the study was to determine the effect of ionizing radiation (IR) on PK-M2-mediated metabolic changes in TNBC cells, and their survival. In addition, we determine the effect of PK-M2 activators on breast cancer stem cells, a radioresistant subpopulation of breast cancer stem cells.

methodsGlucose uptake, lactate production, and glutamine consumption were assessed. The cellular localization of PK-M2 was evaluated by western blot and confocal microscopy. The small molecule activator of PK-M2, TEPP46, was used to promote its pyruvate kinase function. Finally, effects on cancer stem cell were evaluated via sphere forming capacity.

resultsExposure of TNBC cells to IR increased their glucose uptake and lactate production. As expected, PK-M2 expression levels also increased, especially in the nucleus, although overall pyruvate kinase activity was decreased. PK-M2 nuclear localization was shown to be associated with breast cancer stem cells, and activation of PK-M2 by TEPP46 depleted this population.

conclusionsRadiotherapy can induce metabolic changes in TNBC cells, and these changes seem to be mediated, at least in part by PK-M2. Importantly, our results show that activators of PK-M2 can deplete breast cancer stem cells in vitro. This study supports the idea of combining PK-M2 activators with radiation to enhance the effect of radiotherapy in resistant cancers, such as TNBC.

Indexed as

Carrier ProteinsCell Line, TumorCell NucleusFemaleGene Expression Regulation, NeoplasticGlucoseHumansLactic AcidMembrane ProteinsNeoplastic Stem CellsRadiation, IonizingThyroid Hormone-Binding ProteinsThyroid HormonesTriple Negative Breast NeoplasmsUp-RegulationCarrier ProteinsGlucoseLactic AcidMembrane ProteinsThyroid Hormone-Binding ProteinsThyroid HormonesBreast cancerMetabolismPyruvate kinaseRadiation therapy

Identifiers

PMID31372790
PMCPMC6790295
OpenAlexW2965036896

What OpenQuestion holds

Textmetadata
LicenceTDM
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.