Evidence map›Paper›PMID 41145774›Full record

ArticleNature cancer2025

SCRN1 confers hepatocellular carcinoma resistance to ferroptosis by stabilizing GPX4 via STK38-mediated phosphorylation.

Yijie Tao, Shulei Yin, Kai Wei, Liyuan Zhao, Yani Cui, Chunzhen Li, Yunyang Wu, Panpan Hu, Shenhui Yin, Likun Cui and 14 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. 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

24 authors.

Yijie Tao *National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Shulei Yin *National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Kai Wei *Department of Anesthesiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.ORCID http://orcid.org/0009-0004-3986-3855
Liyuan Zhao *National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Yani CuiNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Chunzhen LiNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Yunyang WuSchool of Traditional Chinese Medicine, Naval Medical University, Shanghai, China.
Panpan HuNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Shenhui YinNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Likun CuiNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Yunyan ZhangDepartment of Respiratory and Critical Care Medicine, Changzheng Hospital, Naval Medical University, Shanghai, China.
Yixian HeNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Shu YuNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Jie ChenNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Shaoteng LuNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Guifang QiuNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Mengqi SongNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Siqi YangNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Qianshan HouNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Yiquan XueNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Chen QianNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Sheng XuNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China. xusheng@immunol.org.ORCID http://orcid.org/0000-0002-9547-8052
Yizhi YuNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China. yuyz@immunol.org.ORCID http://orcid.org/0000-0002-3793-1154
Zui ZouNational Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China. zouzui@smmu.edu.cn.ORCID http://orcid.org/0000-0002-8433-8388

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32400760National Natural Science Foundation of China (National Science Foundation of China) 81871253National Natural Science Foundation of China (National Science Foundation of China) 82071789National Natural Science Foundation of China (National Science Foundation of China) 82101854National Natural Science Foundation of China (National Science Foundation of China) 82371782
6 · The paper itself

Abstract

Systemic therapy is the optimal choice for individuals with unresectable or advanced hepatocellular carcinoma (HCC). However its effectiveness is constrained by resistance. Ferroptosis is a unique form of regulated cell death and plays an essential role in HCC systemic therapy. Here we identified that secernin-1 (SCRN1) was closely associated with ferroptosis resistance and poor prognosis in HCC. Specifically, high expression of SCRN1 enhances the interaction of phosphokinase serine/threonine kinase 38 (STK38) and glutathione peroxidase 4 (GPX4) to promote the phosphorylation of GPX4 at S45. This phosphorylation impairs heat shock protein family A member 8 (HSC70) recognition and degradation of GPX4 by chaperone-mediated autophagy, which further alleviates lipid peroxidation and ferroptosis. Our findings reveal a critical mechanism by which tumor cells antagonize ferroptosis through enhanced GPX4 phosphorylation and provide potential targets and strategies for HCC treatment.

Indexed as

Carcinoma, HepatocellularFerroptosisLiver NeoplasmsPhospholipid Hydroperoxide Glutathione PeroxidaseProtein Serine-Threonine KinasesTumor Suppressor ProteinsAnimalsAutophagyCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansLipid PeroxidationMaleMicePhosphorylationPhospholipid Hydroperoxide Glutathione PeroxidaseProtein Serine-Threonine KinasesTumor Suppressor Proteins

Identifiers

PMID41145774

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.