Evidence map›Paper›PMID 37480151›Full record

ArticleCell & bioscience2023

Copper chelation suppresses epithelial-mesenchymal transition by inhibition of canonical and non-canonical TGF-β signaling pathways in cancer.

Ensieh M Poursani, Daniele Mercatelli, Prahlad Raninga, Jessica L Bell, Federica Saletta, Felix V Kohane, Daniel P Neumann, Ye Zheng, Jourdin R C Rouaen, Toni Rose Jue and 19 more

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

Article in Cell & bioscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
5.5field-weighted citation impact, top 4% 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

25 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
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  7. From copper imbalance to immunometabolic remodeling: cuproptosis-related vulnerability and therapeutic hypotheses in autoimmune diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
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  16. Metal Ion Signaling in Biomedicine.Chemical reviews · 2025
    Review
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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

29 authors at 9 institutions in 3 countries.

Ensieh M Poursani *Children's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia.
Daniele Mercatelli *Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
Prahlad Raninga *QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Jessica L BellChildren's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia.
Federica SalettaChildren's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia.
Felix V KohaneSchool of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
Daniel P NeumannSchool of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
Ye ZhengSchool of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
Jourdin R C RouaenChildren's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia.
Toni Rose JueChildren's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia.
Filip T MichniewiczChildren's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia.
Piper SchadelChildren's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia.
Erin KasiouChildren's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia.
Maria TsoliChildren's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia.
Giuseppe CirilloDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
Shafagh WatersSchool of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
Tyler Shai-HeeChildren's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia.
Riccardo CazzoliChildren's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia.
Merryn BrettleKatharina Gauss Light Microscopy Facility, University of New South Wales, Sydney, NSW, Australia.
Iveta SlapetovaKatharina Gauss Light Microscopy Facility, University of New South Wales, Sydney, NSW, Australia.
Maria KashermanKatharina Gauss Light Microscopy Facility, University of New South Wales, Sydney, NSW, Australia.
Renee WhanKatharina Gauss Light Microscopy Facility, University of New South Wales, Sydney, NSW, Australia.
Fernando Souza-Fonseca-GuimaraesThe University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD, Australia.
Linda VahdatDartmouth Cancer Center, Lebanon, NH, USA.
David ZieglerChildren's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia.
John G LockSchool of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
Federico M GiorgiDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
KumKum Khanna *QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Orazio VittorioChildren's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia. ovittorio@ccia.org.au.
UNSW Sydney · AUChildren's Cancer Institute Australia · AUGarvan Institute of Medical Research · AUQIMR Berghofer Medical Research Institute · AUUniversity of Bologna · ITDartmouth Psychiatric Research Center · USEuropean Institute of Oncology · ITThe University of Queensland · AUUniversity of Calabria · IT

Funding

National Health and Medical Research Council APP1164960
6 · The paper itself

Abstract

backgroundMetastatic cancer cells exploit Epithelial-mesenchymal-transition (EMT) to enhance their migration, invasion, and resistance to treatments. Recent studies highlight that elevated levels of copper are implicated in cancer progression and metastasis. Clinical trials using copper chelators are associated with improved patient survival; however, the molecular mechanisms by which copper depletion inhibits tumor progression and metastasis are poorly understood. This remains a major hurdle to the clinical translation of copper chelators. Here, we propose that copper chelation inhibits metastasis by reducing TGF-β levels and EMT signaling. Given that many drugs targeting TGF-β have failed in clinical trials, partly because of severe side effects arising in patients, we hypothesized that copper chelation therapy might be a less toxic alternative to target the TGF-β/EMT axis.

resultsOur cytokine array and RNA-seq data suggested a link between copper homeostasis, TGF-β and EMT process. To validate this hypothesis, we performed single-cell imaging, protein assays, and in vivo studies. Here, we used the copper chelating agent TEPA to block copper trafficking. Our in vivo study showed a reduction of TGF-β levels and metastasis to the lung in the TNBC mouse model. Mechanistically, TEPA significantly downregulated canonical (TGF-β/SMAD2&3) and non-canonical (TGF-β/PI3K/AKT, TGF-β/RAS/RAF/MEK/ERK, and TGF-β/WNT/β-catenin) TGF-β signaling pathways. Additionally, EMT markers of MMP-9, MMP-14, Vimentin, β-catenin, ZEB1, and p-SMAD2 were downregulated, and EMT transcription factors of SNAI1, ZEB1, and p-SMAD2 accumulated in the cytoplasm after treatment.

conclusionsOur study suggests that copper chelation therapy represents a potentially effective therapeutic approach for targeting TGF-β and inhibiting EMT in a diverse range of cancers.

Indexed as

CancerCopper chelationEMTMetastasisTGF-β signaling pathways

Identifiers

PMID37480151
PMCPMC10362738
OpenAlexW4385064259

What Socratic 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 Socratic graph.