Evidence map›Paper›PMID 34390123›Full record

ArticleMolecular oncology2021

Elesclomol induces copper-dependent ferroptosis in colorectal cancer cells via degradation of ATP7A.

Wei Gao, Zhao Huang, Jiufei Duan, Edouard C Nice, Jie Lin, Canhua Huang

Open access · goldAbstract read
In one paragraph

Article in Molecular oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 222 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
222citing papers in PubMed, 1 pooled it
25.1field-weighted citation impact, top 1% 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

222 citing papers in PubMed, 1 synthesis or guideline pooled it, 319 citations in OpenAlex.

  1. Pooled it
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  12. [Role of glutathione in regulating ferroptosis and cuproptosis in metabolic dysfunction-associated steatotic liver disease].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026
    Review
  13. Review
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  15. Article
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  17. USP9X regulates copper-induced CASP9/CASP3/GSDME-dependent pyroptosis by deubiquitinating JAK1.Apoptosis : an international journal on programmed cell death · 2026
    Article
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  19. Review
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162 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

6 authors at 3 institutions in 2 countries.

Wei GaoState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu, China.
Zhao HuangState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu, China.
Jiufei DuanState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu, China.
Edouard C NiceDepartment of Biochemistry and Molecular Biology, Monash University, Clayton, Australia.
Jie LinDepartment of Medical Oncology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.ORCID 0000-0003-3784-8120
Canhua HuangState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu, China.ORCID 0000-0003-2247-7750
Sichuan University · CNKunming Medical University · CNMonash University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer cells reprogram their copper metabolism to adapt to adverse microenvironments, such as oxidative stress. The copper chelator elesclomol has been reported to have considerable anticancer efficacy, but the underlying mechanisms remain largely unknown. In this study, we found that elesclomol-mediated copper overload inhibits colorectal cancer (CRC) both in vitro and in vivo. Elesclomol alone promotes the degradation of the copper transporter copper-transporting ATPase 1 (ATP7A), which retards the proliferation of CRC cells. This property distinguishes it from several other copper chelators. Combinational treatment of elesclomol and copper leads to copper retention within mitochondria due to ATP7A loss, leading to reactive oxygen species accumulation, which in turn promotes the degradation of SLC7A11, thus further enhancing oxidative stress and consequent ferroptosis in CRC cells. This effect accounts for the robust antitumour activity of elesclomol against CRC, which can be reversed by the administration of antioxidants and ferroptosis inhibitors, as well as the overexpression of ATP7A. In summary, our findings indicate that elesclomol-induced copper chelation inhibits CRC by targeting ATP7A and regulating ferroptosis.

Indexed as

Colorectal NeoplasmsFerroptosisCopperCopper-Transporting ATPasesHumansHydrazinesPeptide FragmentsTumor MicroenvironmentATP7A protein, humanATP7A protein, human (2-79)CopperCopper-Transporting ATPaseselesclomolHydrazinesPeptide FragmentsATP7Acolorectal cancercopperelesclomolferroptosis

Identifiers

PMID34390123
PMCPMC8637554
OpenAlexW3190196675

What OpenQuestion 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 OpenQuestion graph.