Evidence map›Paper›PMID 34162423›Full record

ArticleJournal of experimental & clinical cancer research : CR2021

Metformin induces Ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer.

Jingjing Yang, Yulu Zhou, Shuduo Xie, Ji Wang, Zhaoqing Li, Lini Chen, Misha Mao, Cong Chen, Aihua Huang, Yongxia Chen and 4 more

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

Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 241 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
241citing papers in PubMed, 4 pooled it
36.5field-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

241 citing papers in PubMed, 4 syntheses or guidelines pooled it, 360 citations in OpenAlex.

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  17. The mechanistic basis and cellular functions of UFMylation.Nature reviews. Molecular cell biology · 2026
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181 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

14 authors at 2 institutions in 1 country.

Jingjing YangDepartment of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310000, Zhejiang, China.
Yulu ZhouDepartment of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310000, Zhejiang, China.
Shuduo XieDepartment of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310000, Zhejiang, China.
Ji WangDepartment of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310000, Zhejiang, China.
Zhaoqing LiDepartment of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310000, Zhejiang, China.
Lini ChenDepartment of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310000, Zhejiang, China.
Misha MaoDepartment of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310000, Zhejiang, China.
Cong ChenDepartment of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310000, Zhejiang, China.
Aihua HuangDepartment of Pathology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310000, Zhejiang, China.
Yongxia ChenDepartment of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310000, Zhejiang, China.
Xun ZhangDepartment of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310000, Zhejiang, China.
Noor Ul Hassan KhanZhejiang University School of Medicine, Hangzhou, 310031, Zhejiang, China.
Linbo WangDepartment of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310000, Zhejiang, China. linbowang@zju.edu.cn.
Jichun ZhouDepartment of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310000, Zhejiang, China. jichun-zhou@zju.edu.cn.
Sir Run Run Shaw Hospital · CNZhejiang University · CN

Funding

National Natural Science Foundation of China No. 81972453, No. 81972597, No. 81602471 and No. 81672729Natural Science Foundation of Zhejiang Province LY19H160055, LY19H160059, LY18H160005, and LY20H160026Zhejiang Provincial Key Laboratory of Wood Science and Technology (CN) No. 2021RC016
6 · The paper itself

Abstract

backgroundFerroptosis is a newly defined form of regulated cell death characterized by the iron-dependent accumulation of lipid peroxidation and is involved in various pathophysiological conditions, including cancer. Targeting ferroptosis is considered to be a novel anti-cancer strategy. The identification of FDA-approved drugs as ferroptosis inducers is proposed to be a new promising approach for cancer treatment. Despite a growing body of evidence indicating the potential efficacy of the anti-diabetic metformin as an anti-cancer agent, the exact mechanism underlying this efficacy has not yet been fully elucidated.

methodsThe UFMylation of SLC7A11 is detected by immunoprecipitation and the expression of UFM1 and SLC7A11 in tumor tissues was detected by immunohistochemical staining. The level of ferroptosis is determined by the level of free iron, total/lipid Ros and GSH in the cells and the morphological changes of mitochondria are observed by transmission electron microscope. The mechanism in vivo was verified by in situ implantation tumor model in nude mice.

resultsMetformin induces ferroptosis in an AMPK-independent manner to suppress tumor growth. Mechanistically, we demonstrate that metformin increases the intracellular Fe

conclusionsThis study is the first to demonstrate that the ability of metformin to induce ferroptosis may be a novel mechanism underlying its anti-cancer effect. In addition, we identified SLC7A11 as a new UFMylation substrate and found that targeting the UFM1/SLC7A11 pathway could be a promising cancer treatment strategy.

Indexed as

Amino Acid Transport System y+AnimalsAntineoplastic AgentsBreast NeoplasmsCell Line, TumorFemaleFerroptosisGene Expression Regulation, NeoplasticHumansLipid PeroxidationMCF-7 CellsMetforminMethylationMiceProteinsTreatment OutcomeAmino Acid Transport System y+Antineoplastic AgentsMetforminProteinsSLC7A11 protein, humanUFM1 protein, humanBreast cancerFerroptosisMetforminSLC7A11UFMylation

Identifiers

PMID34162423
PMCPMC8223374
OpenAlexW3163145088

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.