Evidence map›Paper›PMID 35523770›Full record

ArticleCell death discovery2022

The AMPK-related kinase NUAK2 suppresses glutathione peroxidase 4 expression and promotes ferroptotic cell death in breast cancer cells.

Tanu Singh, Alexander Beatty, Jeffrey R Peterson

Open access · goldAbstract read
In one paragraph

Article in Cell death discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

8 citing papers in PubMed, 14 citations in OpenAlex.

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  8. System XFrontiers in pharmacology · 2022
    Review
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

3 authors at 1 institution in 1 country.

Tanu SinghCancer Signaling & Epigenetics Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
Alexander BeattyCancer Signaling & Epigenetics Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
Jeffrey R PetersonCancer Signaling & Epigenetics Program, Fox Chase Cancer Center, Philadelphia, PA, USA. jeffrey.peterson@fccc.edu.ORCID http://orcid.org/0000-0002-0604-718X
Fox Chase Cancer Center · US

Funding

WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Dietmar J Kappes · 1985 to 2026
$138.8M
Specificity of Effector Activation by Rho Family GTPasesR01GM083025 · NIGMS · RESEARCH INST OF FOX CHASE CAN CTR · PI PETERSON, JEFFREY R · 2008 to 2018
$3.2M
NCI NIH HHS P30 CA006927NIGMS NIH HHS R01 GM083025United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP) W81XWH-19-1-0481
6 · The paper itself

Abstract

Ferroptosis is a caspase-independent form of regulated cell death strongly linked to the accumulation of reactive lipid hydroperoxides. Lipid hydroperoxides are neutralized in cells by glutathione peroxidase 4 (GPX4) and inhibitors of GPX4 are potent ferroptosis inducers with therapeutic potential in cancer. Here we report that siRNA-mediated silencing of the AMPK-related kinase NUAK2 suppresses cell death by small-molecule inducers of ferroptosis but not apoptosis. Mechanistically we find that NUAK2 suppresses the expression of GPX4 at the RNA level and enhances ferroptosis triggered by GPX4 inhibitors in a manner independent of its kinase activity. NUAK2 is amplified along with MDM4 in a subset of breast cancers, particularly the claudin-low subset, suggesting that this may predict vulnerability to GPX4 inhibitors. These findings identify a novel pathway regulating GPX4 expression as well as ferroptotic sensitivity with potential as a biomarker of breast cancer patients that might respond to GPX4 inhibition as a therapeutic strategy.

Identifiers

PMID35523770
PMCPMC9076840
OpenAlexW4229074895

What OpenQuestion holds

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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.