Evidence map›Paper›PMID 31932435›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

Single-cell tracking demonstrates copper chaperone Atox1 to be required for breast cancer cell migration.

Stéphanie Blockhuys, Xiaolu Zhang, Pernilla Wittung-Stafshede

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 2 pooled it
6.3field-weighted citation impact, top 2% 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

82 citing papers in PubMed, 2 syntheses or guidelines pooled it, 133 citations in OpenAlex.

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  16. Copper Homeostasis, Emerging Central Players in Cancer Immunotherapy.Journal of cellular and molecular medicine · 2025
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22 more citing papers are in PubMed but not listed here.

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.

Stéphanie BlockhuysDepartment of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden steblo@chalmers.se pernilla.wittung@chalmers.se.
Xiaolu ZhangDepartment of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden.
Pernilla Wittung-StafshedeDepartment of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden steblo@chalmers.se pernilla.wittung@chalmers.se.ORCID 0000-0003-1058-1964
Chalmers University of Technology · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Copper ions are needed for several hallmarks of cancer. However, the involved pathways, mechanisms, and copper-binding proteins are mostly unknown. We recently found that cytoplasmic Antioxidant 1 copper chaperone (Atox1), which is up-regulated in breast cancer, is localized at the lamellipodia edges of aggressive breast cancer cells. To reveal molecular insights into a putative role in cell migration, we here investigated breast cancer cell (MDA-MB-231) migration by video microscopy as a function of Atox1. Tracking of hundreds of individual cells (per condition) over a 9-h time series revealed that cell migration velocity and directionality are significantly reduced upon Atox1 silencing in the cells. Because silencing of the copper transporter ATP7A also reduced cell migration, these proteins appear to be on the same pathway, suggesting that their well-known copper transport activity is involved. In-cell proximity ligation assays demonstrated that Atox1, ATP7A, and the proenzyme of lysyl oxidase (LOX; copper-loaded via ATP7A) are all in close proximity and that LOX activity is reduced upon Atox1 silencing in the cells. Since LOX is an established player in cancer cell migration, our results imply that Atox1 mediates breast cancer cell migration via coordinated copper transport in the ATP7A-LOX axis. Because individual cell migration is an early step in breast cancer metastasis, Atox1 levels in tumor cells may be a predictive measure of metastasis potential and serve as a biomarker for copper depletion therapy.

Indexed as

Cell MovementGene Expression Regulation, NeoplasticBreast NeoplasmsCell TrackingCopperCopper-Transporting ATPasesCopper Transport ProteinsFemaleHumansMolecular ChaperonesProtein-Lysine 6-OxidaseSingle-Cell AnalysisTumor Cells, CulturedATOX1 protein, humanATP7A protein, humanCopperCopper-Transporting ATPasesCopper Transport ProteinsLOX protein, humanMolecular ChaperonesProtein-Lysine 6-OxidaseAtox1ATP7Abreast cancercell migrationlive imaging

Identifiers

PMID31932435
PMCPMC6995000
OpenAlexW2998818514

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.