Evidence map›Paper›PMID 38317231›Full record

ArticleBreast cancer research : BCR2024

The novel phosphatase NUDT5 is a critical regulator of triple-negative breast cancer growth.

Jing Qian, Yanxia Ma, William M Tahaney, Cassandra L Moyer, Amanda Lanier, Jamal Hill, Darian Coleman, Negar Koupaei, Susan G Hilsenbeck, Michelle I Savage and 3 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Breast cancer research : BCR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

13 citing papers in PubMed, 15 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 2 countries.

Jing QianDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yanxia MaDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
William M TahaneyDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cassandra L MoyerDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Amanda LanierDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jamal HillDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Darian ColemanDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Negar KoupaeiDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Susan G HilsenbeckLester and Sue Smith Breast Center and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA.
Michelle I SavageDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Brent D G PageFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Abhijit MazumdarDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Powel H BrownDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. PHBrown@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USBaylor College of Medicine · USUniversity of British Columbia · CA

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
UPWARDS Training Program (Underrepresented Minorities Working Towards Research Diversity in Science)R25CA240137 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KEYOMARSI, KHANDAN, WATOWICH, STEPHANIE S · 2020 to 2024
$2.1M
NCI NIH HHS P30 CA016672NCI NIH HHS R25 CA240137NIH HHS P30 CA016672Susan G. Komen KG081694
6 · The paper itself

Abstract

backgroundThe most aggressive form of breast cancer is triple-negative breast cancer (TNBC), which lacks expression of the estrogen receptor (ER) and progesterone receptor (PR), and does not have overexpression of the human epidermal growth factor receptor 2 (HER2). Treatment options for women with TNBC tumors are limited, unlike those with ER-positive tumors that can be treated with hormone therapy, or those with HER2-positive tumors that can be treated with anti-HER2 therapy. Therefore, we have sought to identify novel targeted therapies for TNBC. In this study, we investigated the potential of a novel phosphatase, NUDT5, as a potential therapeutic target for TNBC.

methodsThe mRNA expression levels of NUDT5 in breast cancers were investigated using TCGA and METABRIC (Curtis) datasets. NUDT5 ablation was achieved through siRNA targeting and NUDT5 inhibition with the small molecule inhibitor TH5427. Xenograft TNBC animal models were employed to assess the effect of NUDT5 inhibition on in vivo tumor growth. Proliferation, death, and DNA replication assays were conducted to investigate the cellular biological effects of NUDT5 loss or inhibition. The accumulation of 8-oxo-guanine (8-oxoG) and the induction of γH

resultsIn this study, we demonstrated the significant role of an overexpressed phosphatase, NUDT5, in regulating oxidative DNA damage in TNBCs. Our findings indicate that loss of NUDT5 results in suppressed growth of TNBC both in vitro and in vivo. This growth inhibition is not attributed to cell death, but rather to the suppression of proliferation. The loss or inhibition of NUDT5 led to an increase in the oxidative DNA lesion 8-oxoG, and triggered the DNA damage response in the nucleus. The interference with DNA replication ultimately inhibited proliferation.

conclusionsNUDT5 plays a crucial role in preventing oxidative DNA damage in TNBC cells. The loss or inhibition of NUDT5 significantly suppresses the growth of TNBCs. These biological and mechanistic studies provide the groundwork for future research and the potential development of NUDT5 inhibitors as a promising therapeutic approach for TNBC patients.

Indexed as

PyrophosphatasesTriple Negative Breast NeoplasmsAnimalsCell Line, TumorCell ProliferationFemaleHumansReceptors, EstrogenNUDT5 protein, humanPyrophosphatasesReceptors, EstrogenOxidative stressPhosphataseTriple-negative breast cancer

Identifiers

PMID38317231
PMCPMC10845800
OpenAlexW4391541178

What OpenQuestion holds

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LicenceCC BY
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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.