Evidence map›Paper›PMID 39880844›Full record

ArticleNature communications2025

VSTM2L protects prostate cancer cells against ferroptosis via inhibiting VDAC1 oligomerization and maintaining mitochondria homeostasis.

Juan Yang, Xiao Lu, Jing-Lan Hao, Lan Li, Yong-Tong Ruan, Xue-Ni An, Qi-Lai Huang, Xiao-Ming Dong, Ping Gao

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
–field-weighted citation impact
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

27 citing papers in PubMed.

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  15. Autophagy regulation of pyroptosis and ferroptosis: a new strategy for colorectal cancer treatment.Apoptosis : an international journal on programmed cell death · 2026
    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

9 authors.

Juan Yang *College of Life Sciences, Shaanxi Normal University, 710119, Xi'an, China.ORCID http://orcid.org/0000-0003-3857-8521
Xiao Lu *College of Life Sciences, Shaanxi Normal University, 710119, Xi'an, China.
Jing-Lan HaoCollege of Life Sciences, Shaanxi Normal University, 710119, Xi'an, China.ORCID http://orcid.org/0000-0001-6490-2271
Lan LiCollege of Life Sciences, Shaanxi Normal University, 710119, Xi'an, China.
Yong-Tong RuanCollege of Life Sciences, Shaanxi Normal University, 710119, Xi'an, China.
Xue-Ni AnCollege of Life Sciences, Shaanxi Normal University, 710119, Xi'an, China.
Qi-Lai HuangShandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, 266237, China.ORCID http://orcid.org/0000-0002-4252-3980
Xiao-Ming DongCollege of Life Sciences, Shaanxi Normal University, 710119, Xi'an, China. xiaomingdong@snnu.edu.cn.ORCID http://orcid.org/0000-0003-2413-8541
Ping GaoCollege of Life Sciences, Shaanxi Normal University, 710119, Xi'an, China. ping.gao2016@outlook.com.ORCID http://orcid.org/0000-0003-1383-3290

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82472665
6 · The paper itself

Abstract

Ferroptosis is a form of iron-dependent programmed cell death, which is distinct from apoptosis, necrosis, and autophagy. Mitochondria play a critical role in initiating and amplifying ferroptosis in cancer cells. Voltage-Dependent Anion Channel 1 (VDAC1) embedded in the mitochondrial outer membrane, exerts roles in regulation of ferroptosis. However, the mechanisms of VDAC1 oligomerization in regulating ferroptosis are not well elucidated. Here, we identify that a VDAC1 binding protein V-Set and Transmembrane Domain Containing 2 Like (VSTM2L), mainly localized to mitochondria, is positively associated with prostate cancer (PCa) progression, and a key regulator of ferroptosis. Moreover, VSTM2L knockdown in PCa cells enhances the sensitivity of RSL3-induced ferroptosis. Mechanistically, VSTM2L forms complex with VDAC1 and hexokinase 2 (HK2), enhancing their binding affinity and preventing VDAC1 oligomerization, thereby inhibiting ferroptosis and maintaining mitochondria homeostasis in vitro and in vivo. Collectively, our findings reveal a pivotal role for mitochondria-localized VSTM2L in driving ferroptosis resistance and highlight its potential as a ferroptosis-inducing therapeutic target for the treatment of PCa.

Indexed as

FerroptosisMembrane ProteinsMitochondriaProstatic NeoplasmsVoltage-Dependent Anion Channel 1AnimalsCarbolinesCell Line, TumorHexokinaseHomeostasisHumansMaleMiceMice, NudeProtein MultimerizationCarbolinesHexokinaseHK2 protein, humanMembrane ProteinsRSL3 compoundVDAC1 protein, humanVoltage-Dependent Anion Channel 1

Identifiers

PMID39880844
PMCPMC11779845

What OpenQuestion holds

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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.